Receptor In Renal Cell Carcinoma Research Articles

MiR-125b promotes migration and invasion by targeting the vitamin D receptor in renal cell carcinoma.

Purpose: To investigate the expression of miR-125b and vitamin D receptor (VDR) in renal cell carcinoma (RCC) and assess the biological function of miR-125b in RCC.Methods: We used quantitative real-time polymerase chain reaction (RT-PCR) to detect the expression of nucleic acids and western blotting to analyze the protein abundance in RCC cell lines. MiR-125b mimic and inhibitor were employed to investigate the function and behavior of miR-125b in RCC cell lines. The relationship between miR-125 and VDR was verified using luciferase assays.Results: Overexpression of miR-125b promoted migration and invasion and prevent cell apoptosis in ACHN cells. In contrast, miR-125b deficiency suppressed migration and invasion and induced cell apoptosis in 786-O cells. Luciferase assays indicated the interaction between miR-125b and VDR. In collected samples, miR-125b was significantly higher in RCC tissues and negatively correlated to VDR (r=-0.444, p=0.04).Conclusion: MiR-125b displays an oncogene profile in RCC, patients with high expression of miR-125b should be a more frequent follow-up. MiR-125B may be a potential therapeutic target for RCC.

The Role of Chemokine Receptor CXCR3 and Its Ligands in Renal Cell Carcinoma.

The major invasive subtype of kidney cancer is renal cell carcinoma (RCC). The essential components of cancer development are chronic inflammation and neoangiogenesis. It has been suggested that the chemokine ligand 9, -10, –11 (CXCL9–11) and chemokine receptor 3 (CXCR3) chemokines receptor expressed on monocytes, T and NK cells may be involved in the inhibition of angiogenesis. However, to date, little is known about the potential clinical significance of these chemokines and their receptor in renal cell carcinoma. Therefore, in this review, we described the role of CXCR3 and its ligands in pathogenesis of RCC. We performed an extensive search of the current literature in our investigation, using the MEDLINE/PubMed database. The changes of chemokines and their specific receptor in renal cell carcinoma were observed. Published studies revealed an increased expression of CXCR3 and elevated concentration of its ligands in RCC. The association between treatment of RCC and CXCL9–11/CXCR3 concentration and expression was also observed. Moreover, CXCR3 and its ligands levels were related to patient’s prognosis, risk of metastasis and tumor growth. This review describes the potential role of CXCR3 and its ligands in pathogenesis of RCC, as well as their potential immune-therapeutic significance. However, future studies should aim to confirm the clinical and prognostic role of CXCL9–11/CXCR3 in renal cell carcinoma.

LncRNA-SARCC sensitizes osteosarcoma to cisplatin through the miR-143-mediated glycolysis inhibition by targeting Hexokinase2.

Chemotherapy is one of the primary treatments used against cancer. Cisplatin is a conventional chemotherapy drug used to treat osteosarcoma; however, due to the development of cisplatin resistance, advantageous therapeutic outcomes and prognosis of osteosarcoma remain low. Thus, investigation of the specific targeted therapies to circumvent the anti-chemoresistance of osteosarcoma depends on understanding the molecular mechanisms underlying cisplatin resistance. Tumor cells display an increased utilization of glycolysis rather than oxidative phosphorylation. This phenomenon is called the "Warburg effect," which presents a survival advantage for tumor cells, leading to chemoresistance. To date, the molecular mechanism underlying osteosarcoma cisplatin resistance remains to be fully elucidated. In this study, we reported the significant down-regulation of the long noncoding RNA-Suppressing Androgen Receptor in Renal Cell Carcinoma (lncRNA-SARCC) in the cells of osteosarcoma and in the specimens from osteosarcoma patients. Moreover, we observed a negative correlation between the lncRNA-SARCC and cisplatin resistance in the osteosarcoma tissues. Overexpression of the lncRNA-SARCC sensitizes osteosarcoma cells to cisplatin. From microarray analysis, we screened several miRNAs, which are significantly regulated by the lncRNA-SARCC in osteosarcoma cells, and revealed that lncRNA-SARCC promoted microRNA-43 (miR-143) expression in osteosarcoma. Interestingly, miR-143 showed the same expression pattern with the lncRNA-SARCC in osteosarcoma patient specimens. By establishing a cisplatin-resistant cell line from Sarcoma Osteogenic-2 (Saos-2), we found the cisplatin-resistant cells with down-regulated expressions of the lncRNA-SARCC and miR-143, but with a higher glycolysis rate compared to that in parental cells. We identified the glycolysis key enzyme, Hexokinase 2 (HK2), as a direct target for miR-143 in osteosarcoma. Restoration of the HK2 expression in the lncRNA-SARCC-overexpressing osteosarcoma cells reversed cisplatin resistance, suggesting that lncRNA-SARCC-mediated cisplatin sensitivity may be via glycolysis in the miR-143-inhibited osteosarcoma cells. Finally, results from both in vitro and in vivo xenograft models demonstrated that the lncRNA-SARCC was an effective therapeutic agent for overcoming cisplatin resistance in osteosarcoma. Our findings suggest an essential axis of the lncRNA-SARCC-miR-143-HK2 in regulation of osteosarcoma chemosensitivity, presenting the lncRNA-SARCC as a new therapeutic target against cisplatin-resistant osteosarcoma.

Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2α/C-MYC axis under hypoxia.

It is well established that hypoxia contributes to tumor progression in a hypoxia inducible factor-2α (HIF-2α)-dependent manner in renal cell carcinoma (RCC), yet the role of long noncoding RNAs (LncRNAs) involved in hypoxia-mediated RCC progression remains unclear. Here we demonstrate that LncRNA-SARCC (Suppressing Androgen Receptor in Renal Cell Carcinoma) is differentially regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner both in RCC cell culture and clinical specimens. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells. Mechanism dissection reveals that LncRNA-SARCC can post-transcriptionally regulate androgen receptor (AR) by physically binding and destablizing AR protein to suppress AR/HIF-2α/C-MYC signals. In return, HIF-2α can transcriptionally regulate the LncRNA-SARCC expression via binding to hypoxia-responsive elements on the promoter of LncRNA-SARCC. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2α signaling may then lead to differentially modulated RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2α/C-MYC signals against RCC progression.

Increased Expression of Androgen Receptor mRNA in Human Renal Cell Carcinoma Cells is Associated with Poor Prognosis in Patients with Localized Renal Cell Carcinoma

The role of androgen receptor in renal cell carcinoma is not well understood. In this study the correlation between androgen receptor mRNA expression and clinicopathological features in patients with localized renal cell carcinoma was investigated. Additionally, human renal cell carcinoma cell lines were examined for the presence and effect of androgen receptor. Androgen receptor mRNA expression was evaluated by quantitative real-time polymerase chain reaction in 115 tumor samples from patients with primary pathological stage T1 or T2 (pT1/pT2) renal cell carcinoma and 57 specimens of corresponding normal kidney tissue. Reverse transcriptase-polymerase chain reaction and Western blot were done to examine the expression of androgen receptor in human renal cell carcinoma cell lines. Effects on cellular proliferation were investigated after activating and blocking androgen signaling in tissue culture. Androgen receptor mRNA expression levels were significantly higher inpatients with pT2 tumors than in those with pT1 tumors (p = 0.011). Kaplan-Meier estimates revealed significant differences in time to progression and cancer specific survival between low and high androgen receptor mRNA expression groups regardless of gender. Multivariate Cox regression analysis demonstrated that the level of androgen receptor expression was an independent predictor of cancer specific survival (HR 15.546, 95% CI 1.320-183.131, p=0.029). In tissue culture treatment with dihydrotestosterone caused proliferation in androgen receptor positive cell lines while enzalutamide resulted in reduced cell viability in a dose dependent manner. In patients with localized renal cell carcinoma the androgen receptor mRNA expression level is associated with prognosis. In addition, cell culture data suggest that enzalutamide may have an effect in limiting the growthof androgen receptor positive renal cell carcinoma.

Leucine-rich Repeat and Immunoglobulin Domain-containing Protein-1 (Lrig1) Negative Regulatory Action toward ErbB Receptor Tyrosine Kinases Is Opposed by Leucine-rich Repeat and Immunoglobulin Domain-containing Protein 3 (Lrig3)

Lrig1 is the founding member of the Lrig family of transmembrane leucine-rich repeat proteins, which also includes Lrig2 and Lrig3. Lrig1 is a negative regulator of oncogenic receptor tyrosine kinases, including ErbB and Met receptors, and promotes receptor degradation. Lrig1 has recently emerged as both a tumor suppressor and a key regulator of epidermal and epithelial stem cell quiescence. Despite this, little is known of the mechanisms by which Lrig1 is regulated. Lrig3 was recently reported to increase ErbB receptor expression suggesting that it may function in a manner opposite to Lrig1. In this study, we explore the interaction between Lrig1 and Lrig3 and demonstrate that Lrig1 and Lrig3 functionally oppose one another. Lrig3 opposes Lrig1 negative regulatory activity and stabilizes ErbB receptors. Conversely, Lrig1 destabilizes Lrig3, limiting Lrig3's positive effects on receptors and identifying Lrig3 as a new target of Lrig1. These studies provide new insight into the regulation of Lrig1 and uncover a complex cross-talk between Lrig1 and Lrig3.

174 DIHYDROTESTOSTERONE ENHANCES RENAL CELL CARCINOMA CELL SURVIVAL THROUGH SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-5 ACTIVATION VIA ANDROGEN RECEPTOR AND/OR GLUCOCORTICOID RECEPTOR

You have accessJournal of UrologyKidney Cancer: Basic Research (I)1 Apr 2013174 DIHYDROTESTOSTERONE ENHANCES RENAL CELL CARCINOMA CELL SURVIVAL THROUGH SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-5 ACTIVATION VIA ANDROGEN RECEPTOR AND/OR GLUCOCORTICOID RECEPTOR Yunlim Kim, Wansuk Kim, Sejun Park, Myungsun Shim, Dalsan You, Cheryn Song, and Hanjong Ahn Yunlim KimYunlim Kim Seoul, Korea, Republic of More articles by this author , Wansuk KimWansuk Kim Busan, Korea, Republic of More articles by this author , Sejun ParkSejun Park Seoul, Korea, Republic of More articles by this author , Myungsun ShimMyungsun Shim Seoul, Korea, Republic of More articles by this author , Dalsan YouDalsan You Seoul, Korea, Republic of More articles by this author , Cheryn SongCheryn Song Seoul, Korea, Republic of More articles by this author , and Hanjong AhnHanjong Ahn Seoul, Korea, Republic of More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1554AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen receptor (AR) and glucocorticoid receptor (GR) mediate the action of steroid hormones in various tissues, including the kidney. Signal transducer and activator of transcription-5 (STAT5) regulates the expression of genes that mediate cell survival, proliferation, and angiogenesis and is activated in various types of malignancies, including renal cell carcinoma (RCC). Although several important transcriptional targets of STAT5 are known, the effect and molecular mechanism of STAT5 are not well elucidated, especially in RCC cells. Therefore, we examined interaction between STAT5 activation and steroid receptor in RCC. METHODS Using clear cell RCC cell lines Caki-2, A498 and SN12C cell viability assay and Western blot for phosphorylated STAT5 was done after dihydrotestosterone (DHT) treatment at various concentration (0.1, 1, 10nM). Endogenous levels of AR, GR and estrogen receptor (ER) were identified by RT-PCR and Western blot. Using AR antagonist (bicalutamide)/GR antagonist (RU486) and AR/GR-specific siRNA, changes in DHT-induced STAT5 activation were assessed. In human primary RCC cells from patients, cell viability and STAT5 activation after treatment of DHT was assessed by Western blot. RESULTS DHT treatment enhanced STAT5 phosphorylation and promoted cell proliferation up to 34.3% in Caki-2, 25.0% in A498 and 15.7% in SN12C, respectively. Endogenous AR was identified strongly in Caki-2 (193 fold relative to SN12C), weakly in A498 (54 fold relative to SN12C), but not in SN12C. GR was identified strongly in A498, weakly in Caki-2 (0.55 fold relative to A498) and SN12C (0.68 fold relative to A498). Pretreatment of bicalutamide/RU486 abolished DHT-induced cell proliferation and STAT5 activation in these cell lines. Similarly, AR/GR-specific siRNA completely suppressed DHT-induced STAT5 activation. In addition, DHT enhanced cell proliferation and STAT5 activation in 75% of human primary RCC cells expressing AR and/or GR. CONCLUSIONS In RCC cells, DHT activated STAT5 enhancing cell survival and proliferation through STAT5 via AR and/or GR. AR and GR may be new therapeutic target in RCC. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e71 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yunlim Kim Seoul, Korea, Republic of More articles by this author Wansuk Kim Busan, Korea, Republic of More articles by this author Sejun Park Seoul, Korea, Republic of More articles by this author Myungsun Shim Seoul, Korea, Republic of More articles by this author Dalsan You Seoul, Korea, Republic of More articles by this author Cheryn Song Seoul, Korea, Republic of More articles by this author Hanjong Ahn Seoul, Korea, Republic of More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

POS-02.85: Overexpression of metastin receptor in renal cell carcinoma: metastin and its receptor are probable targets for the suppression of renal cell carcinoma metastasis

POS-02.85: Overexpression of metastin receptor in renal cell carcinoma: metastin and its receptor are probable targets for the suppression of renal cell carcinoma metastasis

368: The Analysis of Vitamin D Receptor and Retinoid X Receptor in Renal Cell Carcinoma

You have accessJournal of UrologyVideo Session, Sunday, May 22, 2005 10:00 am - 12:00 pm1 Apr 2005368: The Analysis of Vitamin D Receptor and Retinoid X Receptor in Renal Cell Carcinoma Wataru Obara, Ryuichiro Konda, and Tomoaki Fujioka Wataru ObaraWataru Obara More articles by this author , Ryuichiro KondaRyuichiro Konda More articles by this author , and Tomoaki FujiokaTomoaki Fujioka More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34621-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "368: The Analysis of Vitamin D Receptor and Retinoid X Receptor in Renal Cell Carcinoma." The Journal of Urology, 173(4S), p. 101 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 101 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Wataru Obara More articles by this author Ryuichiro Konda More articles by this author Tomoaki Fujioka More articles by this author Expand All Advertisement PDF DownloadLoading ...

Erratum: LRIG1 and epidermal growth factor receptor in renal cell carcinoma: a quantitative RT–RCR and immunohistochemical analysis

Erratum: LRIG1 and epidermal growth factor receptor in renal cell carcinoma: a quantitative RT–RCR and immunohistochemical analysis

Expression of type I interferon receptor in renal cell carcinoma.

Immunohistochemical analysis of INF-R was performed on 110 renal tumors, 25 peritumoral kidney tissues and 10 lymph node metastases. Pathological material was previously studied and classified according to predominant cell type, stage and grade. A statistical analysis was made in order to determine to what extent the immunoexpression of INF-R differed in relation to the histological variables studied. All peritumoral kidney sections, 89/110 tumors and 9/10 metastases proved positive. Membranous expression was related to clear cell carcinomas. Type I INF-R is expressed in RCC, independent of tumor stage and grade, as well as sex, age and survival. INF-R is widely expressed in RCC in any tumoral type, and its expression is preserved in metastatic disease, which may help to target those patients who could benefit from INF therapy.

Hormone Receptor in Renal Cell Carcinoma and Correlation With Clinical Response to Endocrine Therapy

Analyses of hormone receptors in cytosols from 41 renal cell carcinoma specimens were performed by the dextran-coated charcoal technique, using estradiol, synthetic progestin R5020 and synthetic androgen R1881. Binding data were calculated according to the method of Scatchard. Of 41 renal cell carcinomas estradiol receptor was detected in 11, R5020 receptor in 11 and R1881 receptor in 13. No significant correlation between histopathological findings and hormone receptors was observed. Patients were classified into those positive and negative for receptors. The clinical response of endocrine therapy for 17 with advanced residual or metastatic lesions after nephrectomy was studied in regard to the survival rates. Although there was no complete or partial regression in tumor size, the survival rate of patients with 1 or more receptors was significantly higher than that of patients negative for receptors (p less than 0.01). In conclusion, hormonal manipulation in patients with renal cell carcinoma cannot induce an antitumor effect but seems to increase survival in patients with receptors.

Measurement of Progesterone Receptor in Human Renal Cell Carcinoma and Normal Renal Tissue

Progesterone receptor was measured in eight samples of renal cell carcinoma, nine samples of normal renal tissue, and one sample of melanoma tissue. Progesterone receptor was identified in all samples, with the exception of one renal cell carcinoma. Three patients, all with receptor-positive tumors, were treated with medroxyprogesterone acetate for metastatic disease. In one of these patients there was a partial objective response to treatment. Further research regarding progesterone receptor in renal cell carcinoma is indicated.

Measurement of progesterone receptor in human renal cell carcinoma and normal renal tissue.

Progesterone receptor was measured in eight samples of renal cell carcinoma, nine samples of normal renal tissue, and one sample of melanoma tissue. Progesterone receptor was identified in all samples, with the exception of one renal cell carcinoma. Three patients, all with receptor-positive tumors, were treated with medroxyprogesterone acetate for metastatic disease. In one of these patients there was a partial objective response to treatment. Further research regarding progesterone receptor in renal cell carcinoma is indicated.