MTA1 Research Articles

Identification and characterization of metastasis-associated gene/protein 1 (MTA1).

Metastasis is a complex series of sequential events involving several gene products and the regulated expression of several tumor cell genes. Using rat mammary adenocarcinoma cell lines of differing metastatic potentials and a differential complementary DNA (cDNA) hybridization method, our laboratory embarked in 1992 on a project to identify candidate metastasis-associated genes. Among the genes that were found to be abundantly overexpressed in highly metastatic rat cell lines compared to poorly metastatic cell lines, we identified a completely novel gene without any homologous or related genes in the database in 1994. The full-length cDNA of this gene was cloned, sequenced, and named mta1 (metastasis-associated gene 1), and eventually, its human cDNA counterpart, MTA1, was also cloned and sequenced by our group. MTA1 has now been identified as one of the members of a gene family (MTA gene family). The products of the MTA genes, the MTA proteins, are transcriptional co-regulators that function in histone deacetylation and nucleosome remodeling. In this review, we will briefly discuss the researches for the identification and characterization of the mta1 gene, its human counterpart MTA1, and their protein products.

IUGR in rats is associated with changes in placental expression of MTAs

IUGR in rats is associated with changes in placental expression of MTAs

Overexpression of MTA1 promotes invasiveness and metastasis of ovarian cancer cells

To investigate the effect of metastasis-associated gene MTA1 on proliferation and invasion potential of ovarian cancer cell line A2780. The eukaryotic expressing vector pcDNA3. 1-MTA1 was introduced into A2780 cells by gene transfection in vitro. The MTA1 mRNA and protein level in cancer cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and western blot, respectively. The growth activities of cancer cells were detected by trypan blue stain method. The clone formation assay in soft agar was used to observe the proliferation of cancer cells. Wound healing assay and Transwell assay were used to evaluate migration and invasion abilities of cancer cells. And the protein level of bcl-xL in ovarian cancer cells was measured by immunohistochemistry and western blot. The TUNEL assay was performed to study the apoptosis of tumor cells. Seventy-two hours after transfection, the MTA1 expression increased significantly (P<0.01). The up-regulation of MTA1 did not affect the growth activities of cancer cells (P>0.05), but it promoted clone formation, migration and invasion abilities of cancer cells (P<0.01). The cellular expression of bcl-xL increased 65.22%, with a PI value of (71.64±5.96)%. With the up-regulation of MTA1 and bcl-xL level, the apoptotic rate of A2780 cell was decreased. MTA1 gene plays an important role in progression and metastasis of ovarian cancers, which provides an ideal strategy for gene therapy of ovarian cancers.

Establishment of metastatic molecule diagnostic model for hepatocellular carcinoma

Objective To construct the molecular model and screen the key molecules for evaluation of tumor metastatic potential in nude mice bearing hepatocellular carcinoma (HCC) xenografts.Methods Orthotopic HCC models were established by implantation of human HCC cell line MHCC97H xenografts with high metastatic potential.Thirty-six nude mice bearing HCC were randomized into three groups 14 days post-operation,including palliative resection group (samples A,B),sham operation group (sample C1),and control group (sample C2).Six mice in each group were sacrificed by cervical dislocation 14 days after palliative resection.Oligo Tumor Metastasis Microarray (OHS-028) and GEArray Expression Analysis Suite software were adopted for gene analysis.The methods of support vector machine (SVM),gene significance analysis and gene correlation degree analysis were used to find the markers that could differentiate the metastatic potential of HCC.Gene function net was constructed based on the special gene clustering analysis and multi-dimensional scale.The relevance vector machine (RVM) was used to deal with regression and classification problems.Real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) was applied to detect mRNA expression.Results By the method of support vector machine (SVM),we found the markers composed of 12 genes (BAI1,MTA2,MTA1,SMAD2,GNRH1,CDHS,ITGB3,CHD4,GZMA,ITGA7,CXCR4,and TSHR) could differentiate the metastatic potential of HCC with positive predictive rate of 88.9％ and 93.5％ in the groups with high and low metastatic potential respectively.In addition,it was found that MTSS1,transforming growth factor-β1 (TGF-β1),SMAD2,interleukin-1 β (IL-1 β) and matrix metalloproteinase-7 (MMP-7) were situated in the central position of the gene function net with high metastatic potential,which was confirmed by Real-time PCR.Conclusion The constructed molecule diagnostic model and the key molecules may be used to evaluate metastatic potential of HCC. Key words: Carcinoma, hepatocellular ; Molecular model; Invasion ; Metastasis

Effect of siRNA targeting MTA1 on metastasis malignant phenotype of ovarian cancer A2780 cells

Ovarian cancer is the fifth lethal gynecologic malignancy. Metastasis-associated gene 1 (MTA1) is overexpressed in many malignant tumors with high metastatic potential. This study investigated whether down-regulation of MTA1 expression by RNAi in A2780 ovarian cancer cells could affect proliferation, anoikis, migration, invasion and adhesion of the cells and to research the potential for MTA1 gene therapy of ovarian cancer. After transfection with effective Mta1 gene siRNA, the effects on proliferation, anoikis, migration, invasion and adhesion of A2780 cells were tested by MTT assay, flow cytometry, wound-healing assay, Transwell assay and adhesion assay. Expression levels of PTEN, beta 1 integrin, MMP-9, phosphor-AKT (Ser473), and total AKT activity were evaluated in control and transfected cells. The results showed that inhibition of MTA1 mediated by Mta1-siRNA transfection decreased the cell invasion, migration and adhesion, and induced the increased cell anoikis, but no significant difference was found in proliferation of A2780 cancer cells. In addition, beta 1 integrin, MMP-9, and phosphor-AKT protein levels were significantly down-regulated, while PTEN was significantly up-regulated. These results demonstrated that MTA1 played an important role in the cell metastasis in ovarian cancer. MTA1 could serve as another novel potential therapeutic target in ovarian cancer.

Expression of USP22, MTA1 and Ki-67 in esophageal squamous cell carcinoma

目的：探讨泛素特异性肽酶22（ubiquitin specific peptidase 22,USP22）,转移相关基因1（metastasis associated gene 1,MTA1）及细胞增殖核抗原（nuclear associated antigen,Ki-67）在人食管鳞癌组织中的表达、与肿瘤生物学行为的关系以及他们三者之间的相关性.方法：采用免疫组织化学的方法检测USP22、MTA1及Ki-67在人食管鳞癌组织、癌旁组织及正常组织的表达,探讨上述三者在不同组织中表达的特点及他们相互之间的相关性.结果：（1）USP22的阳性表达率：食管鳞癌组织68.18%,癌旁组织36.36%,正常组织15.91%,两两组间比较,均P〈0.05,差异均具有统计学意义;USP22蛋白的阳性表达率与肿瘤浸润深度及组织学分级有显著的关系,而与淋巴结转移、年龄、性别无关;（2）MTA1的阳性表达率：食管鳞癌组织61.36%,癌旁组织31.82%,正常组织6.82%,两两组间比较,均P〈0.05,差异均具有统计学意义;MTA1蛋白的阳性表达率与淋巴结转移、肿瘤浸润深度及组织学分级有显著的关系,而与年龄、性别无关;（3）Ki-67的阳性表达率：食管鳞癌组织70.45%,癌旁组织43.18%,正常组织11.36%,两两组间比较,均P〈0.05,差异均具有统计学意义;Ki-67蛋白的阳性表达率与淋巴结转移、肿瘤浸润深度及组织学分级有显著的关系,而与年龄、性别无关;（4）USP22蛋白的表达与MTA1蛋白的表达呈正相关;USP22蛋白的表达与Ki-67蛋白的表达呈正相关;MTA1蛋白的表达与Ki-67蛋白的表达无相关性.结论：USP22、MTA1及Ki-67参与食管癌的发生发展、浸润转移,三者联合检测将有助于食管癌的诊断,可更准确地判断食管癌的生物学行为,并有望成为食管癌基因治疗的新靶点.

Aberrant Expression Levels of MTA1 and RECK in Nasopharyngeal Carcinoma: Association with Metastasis, Recurrence, and Prognosis

We investigated the expression and clinical value of MTA1 and RECK genes in patients with nasopharyngeal carcinoma (NPC). We examined MTA1 and RECK expression in nasopharyngeal tissue from patients with chronic nasopharyngitis, lymph nodes with metastasis of NPC, and primary NPC tumor tissue by means of in situ hybridization and analyzed their correlation with the clinicopathologic features of NPC. The positive expression of MTA1 in the NPC tissues and metastatic lymph nodes was significantly higher than that in the chronic nasopharyngitis tissues (p < 0.05). The positive expression of RECK in the NPC tissues and metastatic lymph nodes was significantly lower than that in the chronic nasopharyngitis tissues (p < 0.05). The RECK expression level was inversely correlated with the MTA1 expression level in the NPC tissues (p < 0.05). The increased MTA1 and decreased RECK expressions in the NPC tissues had no association with gender, age, T-stage, or clinical stage (p > 0.05). However, they had a positive correlation with cervical lymph node metastasis, tumor recurrence, and 5-year overall survival rate of the patients with NPC (p < 0.05). Moreover, multivariate analysis showed that MTA1 and RECK expressions were independent prognostic factors for survival (p < 0.05). The conversely abnormal expression levels of MTA1 and RECK may be collectively involved in progression of malignancies and may serve as molecular predictors for metastasis, recurrence, and prognosis of NPC.

MTA3 (metastasis associated 1 family, member 3)

Review on MTA3 (metastasis associated 1 family, member 3 ), with data on DNA, on the protein encoded, and where the gene is implicated.

ShRNA-mediated gene silencing of MTA1 influenced on protein expression of ER alpha, MMP-9, CyclinD1 and invasiveness, proliferation in breast cancer cell lines MDA-MB-231 and MCF-7 in vitro

BackgroundMTA1(metastasis associated-1) is a tumor metastasis associated candidate gene and overexpression in many human tumors, including breast cancer. In this study, we investigated depressive effect on MTA1 by MTA1-specific short hairpin RNA(shRNA) expression plasmids in human breast cancer cell lines MDA-MB-231 and MCF-7, and effect on protein levels of ER alpha, MMP-9, cyclinD1, and tumor cell invasion, proliferation.MethodsShRNA expression vectors targeting MTA1 was constructed and transfected into human breast cancer cell lines MDA-MB-231 and MCF-7. The transfection efficiency was evaluated by fluorescence microscopy, mRNA levels of MTA1 were detected by reverse transcription-polymerase chain reaction (RT-PCR), protein levels of ER alpha, MMP-9 and cyclinD1 were detected by Western blotting, respectively. Tumor cells invasive ability were evaluated by Boyden chamber assay, the cells proliferation were evaluated using cell growth curve and MTT analysis, the cell cycle analysis was performed using flow cytometry.ResultsDown-regulation of MTA1 by RNAi approach led to re-expression of ER alpha in ER-negative breast cancer cell lines MDA-MB-231, and reduced protein levels of MMP-9 and CyclinD1, as well as decreased tumor cell invasion and proliferation, more cells were blocked in G0/G1 stage(P < 0.05). However, after inhibiting mRNA levels of MTA1, protein expression of ER alpha, MMP-9, cyclinD1 and the changes of cancer cells invasiveness, proliferation, cells cycle were no statistical difference in ER-positive human breast cancer cell lines MCF-7 (P > 0.05).ConclusionsShRNA targeted against MTA1 could specifically mediate the MTA1 gene silencing and consequentially recover the protein expression of ER alpha, resulting in increase sensitivity of antiestrogens, as well as suppress the protein levels of MMP-9 and cyclinD1 in ER-negative human breast cancer cell lines MDA-MB-231. Silencing effect of MTA1 could efficiently inhibit the invasion and proliferation in MDA-MB-231 cells. The shRNA interference targeted against MTA1 may have potential therapeutic utility in human breast cancer.

Abstract 2433: Hepatitis B virus X protein induces metastasis-associated protein 1 gene expression through promoter methylation

Abstract Expression of metastasis-associated protein 1 (mta1) gene is well correlated with the degree of invasion and lymphatic metastasis in colorectal, hepatocellular and breast carcinomas. Expression of MTA1 was induced by hepatitis B virus X protein (HBx), however, little is known about transcriptional regulation of mta1 gene expression. Here, we reported that 5′-flanking region of MTA1 promoter contains two CpG islands. CpG island 1 and CpG island 2. The CpG island 1 was highly methylated (32.5%) but CpG island 2 (&amp;lt;1%) was not. Using bisulfite-modified direct sequencing, transient expression of HBx led to an increase in methylation of the CpG island 1 up to 48.8 %. In addition, chromatin immunoprecipitation revealed that HBx recruited DNMT3A to CpG island 1 region of MTA1 promoter. In silico analysis of the CpG island 1 predicted an existence of putative p53 binding sequences. We demonstrated that p53 bound to the CpG island 1 by chromatin immunoprecipitation using specific anti-p53 antibody. Further, p53 was pull-downed by DNA probe encoding the p53 binding sequences. However p53 was not pull-downed by the methylated DNA probe using SssI DNA methyltransferase. These data showed that HBx induced methylation of CpG island 1, which interferes the DNA binding of p53 on the specific DNA region. This result may provide the molecular mechanism of how HBx induces the expression of MTA1 gene. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2433. doi:10.1158/1538-7445.AM2011-2433

Gene Profiling of Mta1 Identifies Novel Gene Targets and Functions

BackgroundMetastasis-associated protein 1 (MTA1), a master dual co-regulatory protein is found to be an integral part of NuRD (Nucleosome Remodeling and Histone Deacetylation) complex, which has indispensable transcriptional regulatory functions via histone deacetylation and chromatin remodeling. Emerging literature establishes MTA1 to be a valid DNA-damage responsive protein with a significant role in maintaining the optimum DNA-repair activity in mammalian cells exposed to genotoxic stress. This DNA-damage responsive function of MTA1 was reported to be a P53-dependent and independent function. Here, we investigate the influence of P53 on gene regulation function of Mta1 to identify novel gene targets and functions of Mta1.MethodsGene expression analysis was performed on five different mouse embryonic fibroblasts (MEFs) samples (i) the Mta1 wild type, (ii) Mta1 knock out (iii) Mta1 knock out in which Mta1 was reintroduced (iv) P53 knock out (v) P53 knock out in which Mta1 was over expressed using Affymetrix Mouse Exon 1.0 ST arrays. Further Hierarchical Clustering, Gene Ontology analysis with GO terms satisfying corrected p-value<0.1, and the Ingenuity Pathway Analysis were performed. Finally, RT-qPCR was carried out on selective candidate genes.Significance/ConclusionThis study represents a complete genome wide screen for possible target genes of a coregulator, Mta1. The comparative gene profiling of Mta1 wild type, Mta1 knockout and Mta1 re-expression in the Mta1 knockout conditions define “bona fide” Mta1 target genes. Further extensive analyses of the data highlights the influence of P53 on Mta1 gene regulation. In the presence of P53 majority of the genes regulated by Mta1 are related to inflammatory and anti-microbial responses whereas in the absence of P53 the predominant target genes are involved in cancer signaling. Thus, the presented data emphasizes the known functions of Mta1 and serves as a rich resource which could help us identify novel Mta1 functions.

Combining siRN A-mediated hTR and hTERT expression in bladder uroepithelium cancer BIU-87 cell lines

Objective To perform a DNA microarray analysis of combining small interfering RNA (siRNA) of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) gene in bladder transitional cell carcinoma cell line BIU-87 telomere Inhibition of enzyme activity. Methods According to the siRNA design principles and TERT.TR gene mRNA coding sequence,respectively,were designed and synthesized three pairs of different and can interfere with TR and TERT gene expression in siRNA sequence and filter out the most efficient suppression sequence ( pRNAT-TERT-Ⅲ: GTACAG-GTTTCACGCATGT gene No. 3229, pRNAT-TR- Ⅲ: CGAAGGTGCCTTGGAATAT gene No. 306). Constructing the hTR,hTERT gene as a target of the joint RNA interference ( RNAi) device pRNAT-TR-Ⅲ+ pRNAT-TERT-Ⅲ(liposome) and transfected into bladder transitional cell carcinoma of BIU-87 cell line, using fluorescent quantitative polymerase chain reaction (PCR) analysis of hTR and hTERT mRNA expression (in the target gene and GAPDH copy number ratios for the relative quantitative analysis) , TRAP-ELJSA detection of telomerase activity (measured A value) ,MTT assay BIU-87 cell growth inhibition (by MTT method Detection of the survival rate of transfected cells) ,and before and after co-RNAi gene chip a-nalysis,using RNA extraction,RNA quality control,cRNA marking and synthesis,chip hybridization, chemi-luminescence detection,image acquisition and data analysis,and further use of part of the reverse transcription (RT)-PCR validation of differentially expressed genes. Results The combined RNA interference hTR and hTERT gene, pRNAT-TERT-Ⅲ+ pRNAT-TR-Ⅲcombined RNAi can specifically inhibit the bladder transitional cell carcinoma cell line BIU-87 in TERT and TR expression (pRNAT-TERT- Ⅲ+ pRNAT-TR-I TERT:0.300 ±0.033 ,P <0.05;TR:0.430 ±0.028,P <0.05). After the combined RNAi and bladder transitional cell carcinoma of BIU-87 cell line growth and telomerase activity were significantly inhibited (pRNAT-TERT-Ⅲ+ pRNAT-TR- Ⅲ: 1.250 ± 0.012, P < 0.05 ). Before and after the joint siRNA gene chip analysis found 21 genes down ( ATM, BAX, BCL2, BCL2L1, BIRC5, CD44, CTNNB1, E2F1, JUN, MCAM, MTA1, MYC, NFKB1, NFKBIA, NME4, PNN, PRKDC, SERP1NE1, THBS1, TNFRSF1A, UCCl). Conclusion The combined RNA interference with hTERT and hTR gene can significantly inhibit bladder cancer BIU-87 cell line growth;joint siRNA inhibited bladder transitional cell carcinoma of BIU-87 cell line causes growth of 21 genes were cut. Key words: Telomerase; siRNA; Bladder transitional cell carcinoma

RNAi silencing MTA1 gene inhibits invasion and migration of esophageal carcinoma cell EC9706

Objective To observe the effect of MTA1 gene silencing by RNA interference on invasion and migration of esophageal carcinoma 9706 cells.

The metastasis-associated genes MTA1 and MTA3 are abundantly expressed in human placenta and chorionic carcinoma cells

Normal placenta development relies on the ability of trophoblast cells to invade into the uterus and to build up an extensively vascularized feto-maternal tissue, necessary for the nutrition of the embryo. The ability of cell migration, invasion, and the ability to induce neovascularization are likewise hallmarks of cancer cells. The metastasis-associated genes MTA1 and MTA3 are known to be involved in cancer cell migration by regulation of cell adhesion proteins and to induce the expression of neoangiogenic cytokines, as recently shown by us for ovarian cancer cells. Therefore, we analyzed the expression of MTA1 and MTA3 in normal human placenta tissues and the chorionic cancer cell lines BeWo, JEG, and JAR. Immunohistochemical analysis revealed a rather strong expression of MTA1 and MTA3 in the nuclei of human trophoblast cells. A high expression level of MTA1 and MTA3 was further observed in the nuclei of human chorionic carcinoma cells, as shown by immunofluorescence analysis, and confirmed by Western blot and RT-PCR analysis. We conclude that the high expression level of MTA proteins in human chorionic cells might facilitate trophoblast cell migration and neoangiogenesis, and might further predispose human chorionic cancer cells with properties that are characteristic for this highly aggressive and metastatic carcinoma type.

The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERβ, and enhances expression of oncogenic cytokine GRO

The metastasis-associated genes MTA1 and MTA3 are transcriptional repressors with potential effects on cancer. We analyzed the expression of MTA1, MTA3, ERα, ERβ, and E-cadherin in a total of 115 paraffin-embedded ovarian cancer tissues with respect to cancer staging and FIGO grading. Expression of MTA1, but not that of MTA3, was found to be significantly enhanced in ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of ovarian cancer. To get further insights into the function of MTA1 in ovarian cancer, MTA1-overexpressing cancer cell clones were generated. In vitro, overexpression of exogenous MTA1 in OVCAR-3 cells had no effect on cell proliferation but enhanced the ability of anchorage-independent growth in soft agar colony formation assays. MTA1 overexpression resulted in downregulation of E-cadherin and MTA3 expression and enhanced expression of the transcriptional repressors SNAIL and SLUG. MTA1 further reduced ERβ expression in vitro and inversely correlated with ERβ expression in vivo. Screening for the expression of angiogenic cytokines expressed by ovarian cancer cells revealed MTA1-mediated upregulation of the oncogenic and angiogenic cytokine GRO (growth-regulated oncogene, CXCL1). Thus, in ovarian cancer, MTA1 expression directly and indirectly regulates the expression of several cancer-promoting as well as metastasis-facilitating factors, indicating an important role for MTA1 expression during ovarian cancer progression.

Inactivation of NuRD Component Mta2 Causes Abnormal T Cell Activation and Lupus-like Autoimmune Disease in Mice

Dynamic changes in chromatin structure through ATP-dependent remodeling and covalent modifications on histones play important roles in transcription regulation. Among the many chromatin modifiers identified, the NuRD (nucleosome remodeling histone deacetylase) complex is unique because it possesses both nucleosome remodeling and histone deacetylase activities. To understand the biological function of the NuRD complex, we generated a knock-out mouse model of the Mta2 (metastasis-associated protein 2) gene, which encodes a NuRD-specific component. Mta2 null mice exhibited partial embryonic lethality. The surviving mice developed lupus-like autoimmune symptoms including skin lesions, bodyweight loss, glomerulonephritis, liver inflammation, and production of autoantibodies. Transplantation of bone marrow cells from Mta2 null mice recapitulated some of the symptoms including skin lesion and bodyweight loss in the recipient mice. Mta2 null T lymphocytes showed normal development but hyperproliferation upon stimulation, which correlates with hyperinduction of interleukin (IL)-2, IL-4, and interferon (IFN)-gamma. T cell hyperproliferation, but not other autoimmune symptoms, was observed in T cell-specific Mta2 knock-out mice. Mta2 null T cells produced more IL-4 and IFN-gamma under Th2 activation conditions, but normal levels of IL-4 and IFN-gamma under Th1 activation conditions. Furthermore, we found that IL-4 is a direct target gene of Mta2. Our study suggests that Mta2/NuRD is involved in modulating IL-4 and IFN-gamma expression in T cell immune responses, and gene expression in non-T cells plays an important role in controlling autoimmunity.

Alteration of ERalpha expression and tumor invasion by RNA interference against metastasis associated-1 gene in human breast cancer cells

To investigate the inhibitory effect on MTA1 gene by MTA1 short hairpin RNA (shRNA), downstream regulation of expression of ERa and invasion of human breast cancer cells. Recombinant plasmid pGenesil-1/MTA1 was constructed and transfected into human breast cancer cell lines MDA-MB-231 and MCF-7. Fluorescence microscopy was used to evaluate the efficacy of transfection. The transcription expression of MTA1 and MMP-9 gene were determined by reverse transcription-polymerase chain reaction (RT-PCR), the protein expression of ERalpha and MMP-9 were determined by immunohistochemical and western blot. The invasion ability was evaluated by Boyden chamber invasive assay. Recombinant plasmid pGenesil-1/MTA1 was constructed and transfected into MDA-MB-231 (82.5%) and MCF-7 (78.2%) successfully. After the transfection, MTA1 mRNA was suppressed in both cell lines (80.2% and 58.7%). The expression of ERalpha protein became positive in transfected MDA-MB-231 cell, and the expression of MMP-9 mRNA were down-regulated. The invasion ability was decreased (27.2% +/- 2.1)% compared with (76.3% +/- 2.4%), (P < 0.05). In contrast, transfected MCF-7 cells failed to show significant difference in the expression of ERalpha and MMP-9, without change of the invasion ability (P > 0.05). RNA interference can effectively suppress the expression of MTA1 in human breast cancer cells. An induction of ERalpha protein and suppression of MMP-9 may be related to the decrease of tumor cell invasive ability. RNA interference involving MTA1 gene may provide an effective anti-cancer gene therapy.

0363: Analysis of Mta1 Gene Expression for Uterine Cervical Cancer By Cdna Microarray and Tissue Array

0363: Analysis of Mta1 Gene Expression for Uterine Cervical Cancer By Cdna Microarray and Tissue Array

Identification and characterization of the variants of metastasis-associated protein 1 generated following alternative splicing

The metastasis-associated gene 1 (mta1) was identified initially in rat highly metastatic cancer cell lines and found to be a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. The gene for mouse mta1 was screened and its genomic structure was determined. It consists of 21 exons spanning 40 kb of genomic DNA. The full-length mouse Mta1 cDNA contained a 2145 nucleotide open reading frame encoding 715 amino acids. In addition to the full-length cDNA, several alternative splicing variants were found. Some differences in the splicing variants found were observed among various mouse organs and cells examined by the semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The cDNAs of the splicing variants were inserted into green fluorescent protein (GFP) expression vector and the subcellular localization of the GFP-Mta1 fusion proteins were analyzed. Knowledge of the Mta1 gene expression pattern will be useful in better understanding its functional diversity.

Reduced MTA1 Expression by RNAi Inhibits in Vitro Invasion and Migration of Esophageal Squamous Cell Carcinoma Cell Line

To distinguish aggressive esophageal squamous cell carcinoma from indolent disease is the important clinical challenge. Studies have indicated that metastasis-associated gene 1(Mta1) played a role in the process of metastasis of carcinoma. The overexpression of Mta1 gene has been found in a variety of tumors. To identify the detailed roles of MTA1 protein in the carcinogenesis of esophageal squamous cell carcinoma, this study analyzed the pathological specimens on tissue microarray derived from 72 patients using immunohistochemistry. MTA1 expression increased in the nuclear with the development of esophageal squamous cell carcinoma from normal epithelial cell, dysplasia, to invasive cancer. In biological studies with human esophageal squamous cell carcinoma cell line, MTA1 plays its roles to promote cancer cell invasion, adhesion and movement. RNA interference (RNAi) against MTA1 decreased the malignant phenotypes. Gene microarray analysis revealed some metastasis-associated genes were altered by MTA1 RNAi. This study started an effective beginning to explore metastasis mechanisms and cancer gene therapy strategy targeting MTA1.