Studies On The Function And Mechanism Of MTA1 Gene In Invasion And Metastasis Of Cervical Cancer

Cancer is the disease seriously threatening the health and survival of people. Till now, the detailed mechanisms on metastasis of cervical cancer are unclear. This study took the metastasis-associated gene 1 (MTA1) as the target to make further understanding about metastasis. The MTA1 product is a component of nuclear remodeling and deacetylation complex (NuRD), which regulates the gene transcription by altering the chromosin status. It is reported that MTA1 is associated with the high metastasis potential in many types of cancer cells.We analyzed the expression of MTA1 and PTEN protein in pathological specimens using immunohistochemistry. The MTA1 protein was located in the nuclei of normal cervical tissues while cervical cancer and metastatic lymph nodes also showed cytoplasmic or membrane expressions besides nuclear expressions. The expression level of MTA1 in cervical cancer tissues and metastatic lymph nodes were significantly higher than that in normal cervical tissues. Overexpression of MTA1 was correlated with lymph node metastasis, the depth of infiltration and vascular involvement. The relationship of MTA1 protein with histological type and tumor differentiation were not found. MTA1 expression levels in cervical cancers were inversely correlated with PTEN protein. Kaplan-Meier survival analysis did not show MTA1 was a prognostic factor.The study in human cervical cancer cell lines showed that MTA1 expression in CaSki cell was higher than that in Hela cell. RNA interference against MTA1 in CaSki cell played its role to decrease cancer cell invasion, adhesion and movement, as well as cell growth and colony formation. Inversely, those cells tranfected with MTA1 high expression plasmid promoted the malignant phenotypes.To make clear the altered molecules in the MTA1 RNAi cell line, we performed RT-PCR study. It revealed that many metastasis-associated genes were up-regulated or down-regulated.We established the subcutaneous implantation model in BALB/c nude mouse with MTA1 treated CaSki cells. Compared with PcDNA-3 plasmid transfected group, PcDNA-MTA1 group with higher expression of MTA1 showed accelerated tumor formation, while the RNAi plasmid transfected group showed delayed tumor formation in the subcutaneous implantation model.In the serial studies, we found MTA1 gene broadly exerts its affection on the cellular biological behavior in cervical cancer cell. MTA1 can promote the metastasis ability of cancer cells and the general outcome of RNAi against MTA1 is to reverse the malignant phenotype. According to our results from animal model, MTA1 may serve as a potential molecule target for cancer gene therapy.