KAI1 Expression Research Articles

The expression and significance of kang ai 1 protein in colorectal adenoma and colorectal carcinoma

Objective To observe the expression and clinical significance of kang ai 1 (Kai1) in the process from the progression from colorectal polyps to cancer, invasion and metastasis. Methods Immunohistochemistry was used to examine the expression of Kai1 in the colorectal tissues, colorectal adenoma tissues and colorectal carcinoma tissues. Real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) was used to detect Kai1 mRNA expression. Results The expression of Kai1 protein was positive in 18 cases of colorectal carcinoma (45.00%), significantly lower than that in colorectal adenoma (91.25%) and colorectal tissues (100.00%), respectively, with significant differences among them (P=0.031). FQ-PCR showed that the expression of Kai1 mRNA in colorectal carcinoma, colorectal adenoma and normal colorectal mucosa was incresed by 2.038±0.933, 9.983±4.337 and 12.260±2.182 respectively (F=11.960, P=0.015). The expression of Kai1 protein and mRNA had a significant correlation with the lymph node metastasis of patients with colorectal carcinoma (P=0.011). Conclusion The abnormal expression of Kai1 protein and mRNA is related with the carcinogenesis and the development of colorectal carcinoma. Key words: Kang ai 1; Colorectal carcinoma; Gene expression

Anti-RhoC siRNAs inhibit the proliferation and invasiveness of breast cancer cells via modulating the KAI1, MMP9, and CXCR4 expression.

Overexpression of RhoC in breast cancer cells indicates poor prognosis. In the present study, we aim to investigate the possible antitumor effects of anti-RhoC small-interfering RNA (siRNA) in inflammatory breast cancer cells. In this study, a specific anti-RhoC siRNA was used to inhibit RhoC synthesis. Transfection of anti-RhoC siRNA into two IBC cells SUM149 and SUM190 induced extensive degradation of target mRNA and led to significant decrease in the synthesis of protein. Anti-RhoC siRNA inhibited cell proliferation and invasion, increased cell apoptosis, and induced cell cycle arrest in vitro. Moreover, the transfection of siRNA increased the expression of KAI1 and decreased the expression of MMP9 and CXCR4 in both mRNA and protein levels. Furthermore, transplantation tumor experiments in BALB/c-nu mice showed that intratumoral injection of anti-RhoC siRNA inhibited tumor growth and increased survival rate. Our results suggested that RhoC gene silencing with specific anti-RhoC siRNA would be a potential therapeutic method for metastatic breast cancer.

KAI-1 and p53 expression in odontogenic cysts: An immunohistochemical (IHC) marker study

Background: KAI-1/CD82 is a tumour suppressor gene; decreased gene expression is associated with the increased invasive ability of oral squamous cell carcinoma (OSCC), as hypothesised for various odontogenic cysts and tumours. p53 protein functions in the G1-S phase of the cell cycle to allow repair of the damaged DNA. In the present study, p53 and KAI-1 expression was investigated by using monoclonal antibodies in the various odontogenic cysts. Aims: To detect KAI-1 and p53 expression in radicular cysts, dentigerous cysts and odontogenic keratocysts (OKCs) and to assess the relation between p53 and KAI-1 expression in the aforementioned cysts. Materials and Methods: The present study included histopathologically diagnosed cases of radicular cysts, dentigerous cysts and OKCs for the expression of KAI-1 and p53 antibodies. Results: Amongst odontogenic cysts, radicular cysts expressed a maximum positivity of KAI-1 (20.92%) while p53 positive cells were maximum in odontogenic keratocysts (4.04%). The correlation between KAI-1 and p53 expression in the various odontogenic cysts was not found to be significant. Conclusion: The increased KAI-1 expression in the radicular cysts and its downregulation in OKCs may be indicative of aggressive clinical behaviour and the fact that OKCs are hypothesised as neoplastic rather than being developmental in origin.

Overexpression of KAI1 inhibits retinoblastoma metastasis in vitro.

The present study aimed to investigate the expression of cluster of differentiation 82 (KAI1), a gene involved in the suppression of tumor metastasis, in human retinoblastoma (RB) tissue and to study the effect of KAI1 expression on RB cell migration and invasion. KAI1 expression was examined in 26 patients with non-invasive and invasive retinoblastoma using reverse transcription-quantitative polymerase chain reaction and western blot analysis. A lentiviral vector containing KAI1 cDNA was used to transfect the two RB cell lines, HXO-Rb44-Gl and Y79. Following successful transfection, the migratory and invasive capacity of the two RB cell lines was evaluated using a Transwell® migration assay. KAI1 expression was observed to be downregulated in invasive RB compared to non-invasive RB. The migratory and invasive capacities of KAI1 transfected cell lines were significantly decreased compared to those of the control cells. KAI1 may be involved in retinoblastoma metastasis, and increased expression of KAI1 significantly inhibits the metastatic ability of RB cells in vitro.

Promoter CpG-Site Methylation of the KAI1 Metastasis Suppressor Gene Contributes to Its Epigenetic Repression in Prostate Cancer.

Repression of the KAI1 metastasis suppressor gene is closely associated with malignancy and poor prognosis in many human cancer types including prostate cancer. Since gene repression in human cancers frequently results from epigenetic alterations by DNA methylation and histone modifications, we examined whether the KAI1 gene becomes silenced through these epigenetic mechanisms in prostate cancer. KAI1 mRNA and protein levels were determined by RT-PCR and immunoblotting analyses, respectively. Methylation status of the KAI1 promoter DNA in prostate cancer cell lines and tissues was evaluated by methylation-specific PCR analysis of bisulfite-modified genomic DNAs. Methylated CpG sites in the KAI1 promoter were identified by sequencing the PCR clones of the bisulfite-modified KAI1 promoter DNA. KAI1 protein levels in human prostate cancer tissue samples were examined by immunofluorescence staining of the tissues with an anti-KAI1 antibody. Among the three human prostate cancer cell lines examined, PC3 and DU145 cells exhibited markedly decreased levels of KAI1 mRNA and protein as compared to LNCaP cells, even though the exogenous KAI1 promoter not being methylated was normally functional in all these cell lines. Treatment of the low KAI1-expressing cell lines with a demethylating agent, 5'-aza-2'-deoxycytidine, significantly elevated KAI1 expression levels, implicating the involvement of DNA methylation in KAI1 downregulation. Methylation of CpG islands within the KAI1 promoter region was observed in the low KAI1-expressing cells, but not in the high KAI1-expressing cells. Also, methyl CpG-binding proteins such as MBD2 and MeCP2 were complexed to the KAI1 promoter in the low KAI1-expressing cells. Bisulfite sequencing analysis identified the intensively methylated CpG residues in the KAI1 promoter clones derived from prostate cancer cells and tissues with no or low KAI1 expression. As in prostate cancer cell lines, prostate cancer tissues from patients also displayed a negative association between KAI1 expression levels and methylation status of the KAI1 promoter. The present data suggest that the KAI1 gene might be repressed by epigenetic alterations through the promoter CpG-site methylation during prostate cancer progression. This epigenetic mechanism could provide a clue for understanding how the KAI1 gene was silenced in metastatic prostate cancers. Prostate 77: 350-360, 2017. © 2016 Wiley Periodicals, Inc.

KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in nasopharyngeal carcinoma cells

ObjectivesThe purpose of this study is to characterize the effect of KAI1 overexpression on the biological behavior of nasopharyngeal carcinoma (NPC) cells. BackgroundNasopharyngeal carcinoma is a highly malignant tumor with a high rate of incidence in China. Currently, there are no ideal therapeutic options for patients with NPC, but a targeted therapy would have great potential for treating it. Therefore, there is an urgent need for novel therapeutic targets to provide new options for treating NPC. The KAI1 gene was originally identified as a metastasis suppressor gene for advanced human cancer. In NPC cell lines and tissues, the expression of KAI1 decreased as the metastatic potential of cells increased, but its potential as a therapeutic target has not been elucidated. MethodsNon-transformed nasopharyngeal epithelium cell NP69 and NPC cell line C666-1 were cultured and KAI1 expression in these cells was detected by qRT-PCR and Western blot. After the transfection of KAI1-pCDNA3.1 to NP69 and C666-1, the KAI1 expression in these cells was detected by qRT-PCR and Western blot, the proliferation was performed by MTS, the cell cycle and apoptosis were performed by flow cytometry, the migration and invasion were examined by transwell. ResultsOur results showed that KAI1 was significantly upregulated in C666-1 cells compared to that in NP69 cells. In addition, KAI1 overexpression significantly inhibited the proliferation, cell cycle, migration, and invasion, and promoted apoptosis of C666-1 cells, but had no significant effect on NP69 cells. ConclusionOur findings suggest that KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in NPC cells. We hypothesize that KAI1 overexpression could be a potential therapeutic target for NPC.

Gadobutrol-dendrimer effects on metastatic and apoptotic gene expression

Dendrimers are one of the most appropriate nanocaries for imaging moieties in imaging applications.The purpose of this study was the evalution of cytotoxicity and inducing apoptosis of dendrimers. This study was conducted in order to investigate the metastasis suppression effect of dendrimer in human breast MCF-7 cell line and finding the nanoparticle protein corona in biological enviromental. Dendrimer cytotoxicity effect was assessed by MTT assay. The mRNA experession level of KAI1 as a metastasis suppressor gene, Bax as Pro- apoptotic gene, Bcl-2 as an anti-apoptotic gene and GAPDH as a housekepping gene were determined by real-time PCR assays.concentration-dependent nanoparticle cytotoxicity effect was proofed at range of 1-2 mg/mL in 24 hours, significant upregulation of mRNA expression of Bax, was observed whereas expression of anti-apoptotic Bcl-2 was down-regulated, also expression of metastasis suppressor gene KAI1 was up-regulated. So far a few studies confirmed apoptosis enhancement effect of dendrimers in MCF-7 cell line via bax/bcl-2 pathways. dendrimer nanoparticles was able to act as metastase inhibitor via upregulation of KAI1 gene.

Nm23-H1 was involved in regulation of KAI1 expression in high-metastatic lung cancer cells L9981

The tetraspanin KAI1/CD82 was identified as a tumor metastasis suppressor that down-regulated in malignant progression of lung cancer. However, the underlying mechanism of anti-metastasis role of KAI1 in lung cancer is hardly known. In this paper, we sought to study the function and regulatory mechanism of KAI1 in high metastasis lung cancer cell line. KAI1 expression was detected in high/low metastatic large lung cancer cell line L9981/NL9980 by quantitative real-time polymerase chain reaction (qRT-PCR). The tumor suppressor function of KAI1 was determined by wound healing assay after over-expression or knockdown of KAI1 in L9981 or NL9980 cells. Invasion assay was performed to detect the invasion ability of L9981 by transfection of KAI1. The effect of tumor suppressor p53 on KAI1 expression was measured by western blot and luciferase assay. Then the regulation of KAI1 due to over-expression of metastasis suppressor nm23-H1 was monitored by qRT-PCR, western blot and reporter gene assay. The progression of L9981 cells after p53 and nm23-H1 expression was detected by invasion assay. Also, methylation status of KAI1 promoter in NL9980 and L9981 cells were examined by bisulfite sequencing and methylation-specific PCR. We found that KAI1 is down-regulated in high metastatic L9981 cells compare with NL9980 cells. The migration and invasion of L9981 cells were remarkably suppressed in vitro by KAI1 transfection. The migration ability of NL9980 was enhanced by inhibition of KAI1. Furthermore, KAI1 expression was induced after over-expression of p53 or nm23-H1, while cell invasion was inhibited in L9981 cells. The results of reporter analysis indicated that KAI1 promoter region between -922 to -846 could response to nm23-H1. In addition, we discovered only slight methylation of KAI1 promoter, which showed that loss expression of KAI1 in L9981 cells may not due to promoter methylation. The results suggested that nm23-H1 was involved in the KAI1-regulated inhibition of metastasis in lung cancer cells. More insights into the relationship between KAI1 and other metastasis suppressors will pave the way for the elucidation of anti-metastasis mechanism in lung cancer.

Immunohistochemical expression pattern of metastasis suppressors KAI1 and KISS1 in endometriosis and normal endometrium

ObjectiveTo analyze the expression pattern of metastasis suppressors KAI1 and KISS1 in the endometrium of patients with and without endometriosis. Study designIn this pilot study, tissue samples were prospectively collected from 38 patients with endometriosis and 29 without endometriosis, undergoing operative laparoscopy in the proliferative phase of the menstrual cycle; diagnosis or absence of endometriosis was confirmed histologically. Protein expression of KAI1 and KISS1 were analyzed immunohistochemically in endometriotic lesions and the eutopic endometrium of patients with endometriosis and without endometriosis. ResultsKAI1 expression was significantly decreased in the glandular eutopic endometrium of endometriosis patients as compared with that of patients without endometriosis (p=0.008). On the other hand, in endometriosis patients, KAI1 expression was significantly increased in the ectopic as compared with the eutopic endometrial stroma (p=0.021). There were no other significant differences in KAI1 expression between different groups. KISS1 expression in the ectopic glandular endometrium was significantly increased as compared with the eutopic glandular endometrium from patients with (p=0.004) and without endometriosis (p=0.008). There was no significant difference in KISS1 protein expression in the stromal endometrium between the three groups. ConclusionsKAI1 and KISS1 are implicated in the pathogenesis and maintenance of endometriosis. Future studies should investigate whether KAI1 and KISS1 could be used as markers for early and minimally invasive detection of endometriosis based on their differential protein expression pattern in the eutopic endometrium of patients with and without endometriosis.

KAI-1 and p53 expression in oral squamous cell carcinomas: Markers of significance in future diagnostics and possibly therapeutics.

Context:KAI-1/CD82 is a tumor suppressor gene with decreased gene expression being associated with increased invasive ability of oral squamous cell carcinomas (OSCCs). p53 protein functions in the G1-S phase of the cell cycle to allow repair of damaged DNA. In the present study, p53 and KAI-1 expression was investigated using monoclonal antibodies in OSCC.Aims:The aim of this study was to detect KAI-1 and p53 expression in OSCCs and to assess the relation between both in OSCCs.Materials and Methods:The present study included histopathologically diagnosed thirty cases of well- and moderately differentiated OSCCs to study the expression of KAI-1 and p53 antibodies.Statistical Analysis:The results obtained were tabulated and statistically analyzed using descriptive statistical analysis; one-way ANOVA; least square difference method and independent t-test.Results:OSCCs exhibited 41.62% positivity for KAI-1 while p53 positive cells were recorded to an extent of 60.82%. A significant positive correlation was observed between KAI-1 and p53 expression in OSCCs.Conclusions:Although a significant amount of work is still required to uncover the mechanisms of action and regulation of KAI-1 and p53 expression, control of the complex metastatic processes would be of interest in controlling the tumor biology in OSCCs as well as other types of malignancies to enhance prognosis in the affected patients and to help protect against future metastasis in the going to be treated and treated patients.

Characteristics of the expression of KAI1/CD82 and PDGFRβ and their impact on glioma progression.

The biological features of glioma cells may define their clinical outcome. Little is known about the interactions between KAI1/CD82 metastatic suppressor protein and PDGFR in gliomas. The aim of the study was to examine KAI1/CD82 and PDGFR expression in gliomas in order to find the impact of these proteins on progression of the tumors. PDGFR, KAI1/CD82 protein expression and mRNA of genes were evaluated on eighty four paraffin-embedded tissue of gliomas using immunohistochemical staining and RT-PCR analysis. The PDGFR expression was higher in IV/III than in I/II glioma grades (p = 0.0004). The level of mRNA PDGFR was associated with the degree of PDGFR immunoreactivity. Downregulation of KAI1/CD82 was associated with tumor malignancy (p = 0.007). The increased level of KAI1/CD82 gene expression (3-4-fold) was found in gliomas with strong KAI1/CD82 immunoreactivity. The parallel KAI1/CD82 and PDGFR expression was more significantly associated with cases in a group graded as III and IV than in a group graded as I/II (p = 0.002). We found that a loss of KAI1/CD82 and an increase in PDGFR expression in gliomas relate to a progressive tumor growth. The correlation between PDGFR and KAI1 expression in high grade gliomas suggests that a direct or indirect interaction between these proteins might have an impact on cell motility and invasive behavior of the tumor.

Expression of PTEN and KAI1 tumor suppressor genes in pancreatic carcinoma and its association with different pathological factors

Pancreatic carcinoma is a common cancer type with a poor prognosis. The aim of the present study was to examine the expression of tumor suppressor genes phosphatase and tensin homolog deleted in chromosome 10 (PTEN) and KAI1 in pancreatic carcinoma and its association with clinical pathological factors. A total of 50 hospitalized cases of pancreatic cancer including 28 males and 22 females aged 31–82 years were included in the present study. Ten cases of normal pancreatic tissue were obtained from cadavers and served as the controls. The pancreatic specimens were embedded in paraffin blocks and slides were prepared for immunohistochemical analysis to determine the expression of PTEN and KAI1 in normal pancreatic tissue and pancreatic carcinoma samples. The positive expression rate of PTEN in the normal pancreatic tissue was higher than that in pancreatic carcinoma (P<0.05), while the positive expression rate of KAI1 in the normal pancreatic tissue was lower than that in pancreatic carcinoma (P<0.05). Pathological factors such as clinical stage of disease, histological grade and the presence or absence of lymphatic metastasis significantly affected the expression of PTEN and KAI1 (P<0.05). In conclusion, the positive expression of PTEN and KAI1 in pancreatic carcinoma is closely associated with the development of pancreatic carcinoma.

Clinicopathological significance of KAI1 expression and epithelial-mesenchymal transition in non-small cell lung cancer.

BackgroundKAI1 and epithelial-mesenchymal transition (EMT) is related to both angiogenesis and lymphangiogenesis and is an important target in new cancer treatment strategies. We aimed to investigate the KAI1 and marker of EMT expression and correlation with lymph node metastasis (LNM) and explore their prognostic impact in non-small cell lung cancer (NSCLC).MethodsTumor tissue specimens from 312 resected patients with stage I–IIIA NSCLC were obtained. Immunohistochemistry was used to assess the expression of the molecular markers KAI1, E-cadherin (E-cad), vimentin, CD34, and D2-40.ResultsThere were 153 N0 and 159 N+ patients. Tumor cell expression of KAI1and the marker of EMT, lymphatic vessel density (LVD), and microvessel density (MVD) were related to LNM. In multivariate analyses, the ages of patients, high tumor cell KAI1 expression, EMT, and the scores of MVD were independent factor of prognosis.ConclusionsTumor cell KAI1 expression, EMT, LVD, and MVD correlate with LNM. Thus, the detection of KAI1, expression of markers of EMT, and the scores of MVD may be used as a potential indicator of NSCLC prognosis.

Abstract A33: Loss of tumor suppressors KAI1 and p27 identifies a unique subgroup of primary melanoma patients with poor survival

Abstract Objective: Melanoma is a highly heterogeneous disease. A certain subgroup of patients with primary melanomas exhibits a greater potential to develop metastatic disease and thus has worse survival. The present study attempts to identify the molecular features shared by metastatic melanomas and the subgroup of primary melanomas, and use the information to assist clinicians to design personalized therapy for primary melanoma patients. Patients and methods: Seven previously reported biomarkers, including BRAF, Dicer, Fbw7, KAI1, MMP2, p27 and Tip60, were investigated. A training cohort with 250 melanoma patients (145 primary melanomas and 105 metastatic melanomas) and an independent cohort with 92 primary melanoma patients were used for the study. Logistic regression analysis was used to identify discriminate biomarkers of metastatic melanoma from primary melanoma. Kaplan-Meier survival and multivariate Cox proportional hazard regression analysis were performed to assess the significance of the molecular signature in the prognosis of melanoma. Results: In the training cohort, we found the loss expression of KAI1 and p27 to be most significant between metastatic and primary melanoma. The primary melanoma patients with loss expression of both KAI1 and p27 had poor 5-year survival in both training cohort (P = 0.002) and independent cohort (P = 0.03). Multivariate Cox regression analysis showed that the KAI1-/p27- signature was an independent factor for disease- specific survival (P = 0.004). More important, compared to KAI1 and p27 as an individual prognostic marker, the KAI1-/p27- signature is more closely associated with melanoma patient survival: the P value is 0.004 for KAI1-/p27-, and 0.044, 0.181 for KAI1 and p27, respectively. Conclusion: Loss of both KAI1 and p27 defines a subgroup of primary melanoma patients with poor prognosis, and the combination signature is better than individual biomarker. The clinical significance of KAI1 and p27 warrants further assessment in prospective clinical trials. Citation Format: Yabin Cheng, Guohong Zhang, Yun Tang, Guangdi Chen, Gholamreza Safaee, Annand Rotte, Magdalena Martinka, Kevin McElwee, Youwen Zhou. Loss of tumor suppressors KAI1 and p27 identifies a unique subgroup of primary melanoma patients with poor survival. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A33.

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis.

Cervical cancer is associated with abnormal expression of multiple genes. Survivin and Bcl-2 proteins are apoptosis inhibitors. The tumor suppressor gene CD82, which encodes the protein KAI1, is downregulated in cervical cancer, and is associated with differentiation degree. We investigated the expression levels of three proteins and their correlation with metastasis in cervical cancer by comparing them in different cervical lesions. Immunohistochemistry was used to detect their three protein expression levels in the normal cervix, chronic cervicitis, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. The relationships between the protein expression levels and tumor type, clinical stage, tissue differentiation, invasion, and metastasis were analyzed. Survivin and Bcl-2 expression levels in cervical cancer were significantly higher than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). KAI1 expression was markedly lower in cervical cancer than in the normal cervix, chronic cervicitis, or CIN (P < 0.05). There was no statistical difference between the expression levels of the three proteins in CIN and chronic cervicitis, but there were differences in expression between CIN and normal cervical tissues (P < 0.05). Bcl-2 and survivin levels were positively correlated while KAI1 expression was negatively correlated with clinical stage. Survivin and KAI1 expression levels were associated with lymph node metastasis (P < 0.05), and KAI1 expression was positively related with differentiation degree (P < 0.05). Survivin, Bcl-2, and KAI1 are metastasis-related factors in cervical cancer. Overexpression of survivin and Bcl-2, and low expression of KAI1 promotes cervical cancer progress and metastasis.

The relationships between the immunoexpression of KAI1, MMP-2, MMP-9 and steroid receptors expression in endometrial cancer.

The role of the parallel expression of the KAI1 protein and metalloproteinases (MMP-2 and MMP-9) in respect to the status of steroid receptors in endometrial cancer is still incompletely understood. The aim of this study was to evaluate the expression of and correlation between KAI1 on one hand and MMP-2 and MMP-9 on the other hand in terms of the status of the estrogen (ER) and progesterone receptors (PR) in 100 patients with endometrial cancer. The expressions of KAI1, MMP-2, MMP-9, ER and PR were assessed immunohistochemically on paraffin-embedded tissues. No correlations were found between these biomarkers and the clinical and pathological parameters of the endometrial cancer. However, in KAI1-positive cases, the expression was limited to a small area of tumor tissue in FIGO stages III-IV. A tendency towards the high expression of MMP-9 and MMP-2 was observed in the advanced stages of endometrial cancer (FIGO IIIA-IV). Positive correlations between the presence of KAI1 and PR and between the presence of MMP-9 and PR were found in endometrial cancer. A positive correlation was also observed between KAI1 and MMP-2 expression, and a borderline one between KAI1 and MMP-9 expression in endometrial cancer. KAI1+/PR+ and KAI1+/ER- immunophenotypes were observed more frequently in FIGO low stages and with well-differentiated tumor grade. However, the KAI1-/ER+ and KAI1-/PR+ immunophenotypes were mainly observed in advanced stages of endometrial cancer. KAI1+/MMP-2+ and KAI1+/MMP-9+ immunophenotypes were observed in FIGO Istage and with well-differentiated tumors. KAI1-/MMP-2+ and KAI1-/MMP-9+ phenotypes were more often observed in FIGO stage II. Our study showed that KAI1 protein, as well as steroid receptors, might modulate MMP-2 and MMP-9 expression in endometrial cancer. Our study revealed that the overlapping expression of the biomarkers investigated here suggests that cooperation between these molecules exists, even at the early stages of endometrial cancer growth, and may determine the speed of tumor cell dissemination and might characterize the biological behavior of endometrial cancer.

Expression characteristics of KAI1 and vascular endothelial growth factor and their diagnostic value for hepatocellular carcinoma.

Background/AimsWe tried to investigate the expression characteristics of KAI1, a suppressor of wide-spectrum tumor metastasis, and vascular endothelial growth factor (VEGF), the most common angiogenesis factor, and then to analyze their diagnostic value for hepatocellular carcinoma (HCC).MethodsThe protein and mRNA expression levels of KAI1 or VEGF in HCC tissues and in self-controlled para-carcinoma tissues were analyzed by Western blot and real-time polymerase chain reaction, respectively. Serum levels of KAI1 and VEGF in the patients with HCC, benign liver disease or in healthy controls were quantitatively detected by enzyme-linked immunosorbent assay.ResultsThe expression level of KAI1 was downregulated, while the expression level of VEGF was upregulated in the tissues or serum of the patients with HCC. The expression level of serum KAI1 in HCC patients was correlated with TNM staging, intrahepatic metastasis, lymph node or peritoneal metastasis, and portal vein thrombus. In addition to the factors that were correlated with KAI1 expression, VEGF expression was also closely related to the α-fetoprotein level of the patients. The area under the receiver operating characteristic curve for the diagnosis of HCC was 0.907 for KAI1 and 0.779 for VEGF. The sensitivity of serum KAI1 levels in the diagnosis of HCC was 86.96%; the accuracy was 83.06%, while the sensitivity, the accuracy and the negative predictive value were improved to 91.86%, 84.68%, and 78.79% according to the combined detection of KAI1 and VEGF, respectively.ConclusionsA combined detection of KAI1 and VEGF may greatly improve the efficiency of diagnosis and form a reliable panel of diagnostic markers for HCC.

Effect of PTEN and KAI1 gene overexpression on the proliferation, metastasis and radiosensitivity of ASPC‑1 pancreatic cancer cells under hypoxic conditions.

The aim of the present study was to investigate the effects of PTEN and KAI1 gene overexpression on the proliferation, metastasis and radiosensitivity of ASPC‑1 pancreatic cancer cells under hypoxic conditions. Recombinant vectors that overexpress PTEN and KAI1 genes were transfected into hypoxic ASPC‑1 cells. Protein expression levels were detected by western blot analysis. An MTT cell growth curve assay and a colony‑forming assay were used to analyze cell proliferation, and a Transwell assay was performed to evaluate the metastatic ability of the cells. Annexin V flow cytometry was used to determinate the apoptotic rate of X-ray-treated ASPC-1 cells. Western blot analysis revealed that PTEN‑ and KAI1‑transfected ASPC-1 cells significantly upregulated PTEN and KAI1 expression. The proliferation of hypoxic ASPC-1 cells was significantly suppressed by PTEN and KAI1. Furthermore, PTEN and KAI1 overexpression inhibited the metastatic ability of hypoxic ASPC‑1 cells. Following X‑ray treatment, the percentage of apoptotic cells increased significantly in the ASPC-1 cells transfected with PTEN and KAI1, which demonstrated that hypoxic ASPC-1 cells were more radiosensitive due to PTEN and KAI1 overexpression. In conclusion, double overexpression of PTEN and KAI1 inhibited the proliferation and metastatic activity, and enhanced apoptosis induced by X‑ray in ASPC‑1 cells under hypoxic conditions, which indicates that PTEN and KAI1 double-expression may have valuable application in pancreatic cancer gene therapy.

Overexpression of KAI1 Protein in Diabetic Skin Tissues.

BackgroundPatients with diabetes mellitus often have a difficult life, suffering from foot ulceration or amputation. Diabetes is characterized by chronic inflammation, and one of the features of inflammation is hypoxia. Recently, it has been reported that KAI1 is a hypoxia target gene. There is no published research on hypoxia-related KAI1 protein levels in human diabetic skin. Therefore, we have investigated the expression of KAI1 protein in diabetic skin tissue in vivo.MethodsThe expression of KAI1 protein was evaluated by western blotting in 6 diabetic skin tissue samples and 6 normal skin samples. Immunohistochemical staining was carried out to identify KAI1 expression.ResultsThe western blotting revealed significantly increased expression of the KAI1 protein in diabetic skin tissues as compared to normal skin tissues. Immunohistochemical examination demonstrated that KAI1 was expressed in all diabetic skin tissues with moderate-to-strong positivity and weakly expressed in normal skin tissues.ConclusionsOur data suggest that a high expression of the KAI1 protein can be observed in diabetic skin tissue. To the best of our knowledge, this is the first report suggesting that KAI1 protein expression in diabetic skin tissues may be associated with chronic inflammatory states and hypoxia.

Differential expression of the metastasis suppressor KAI1 in decidual cells and trophoblast giant cells at the feto-maternal interface

Invasion of trophoblasts into maternal uterine tissue is essential for establishing mature feto-maternal circulation. The trophoblast invasion associated with placentation is similar to tumor invasion. In this study, we investigated the role of KAI1, an anti-metastasis factor, at the maternal-fetal interface during placentation. Mouse embryos were obtained from gestational days 5.5 (E5.5) to E13.5. Immunohistochemical analysis revealed that KAI1 was expressed on decidual cells around the track made when a fertilized ovum invaded the endometrium, at days E5.5 and E7.5, and on trophoblast giant cells, along the central maternal artery of the placenta at E9.5. KAI1 in trophoblast giant cells was increased at E11.5, and then decreased at E13.5. Furthermore, KAI1 was upregulated during the forskolinmediated trophoblastic differentiation of BeWo cells. Collectively, these results indicate that KAI1 is differentially expressed in decidual cells and trophoblasts at the maternal-fetal interface, suggesting that KAI1 prevents trophoblast invasion during placentation. [BMB Reports 2013; 46(10): 507-512]