Aberrant Expression Of MTA2 Protein Promotes The Proliferation And Metastasis Of Breast Cancer Cells By Activating The ERK/MAPK Pathway

Background Breast cancer is the most common malignancy in women and the incidence is rising in our country recently. However, therapeutic options for the treatment of patients with this tumor are limited to 3 fundamental modalities:surgical resection, radiation therapy and chemotherapy. Against advanced carcinomas, therapeutic options are limited to radiation therapy and chemotherapy; however, these modalities do not yield results. Therefore, cancer-specific target therapy may be expected to become a novel treatment modality for breast carcinomas. Metastasis-associated gene family (MTA) includes three members:MTA1, MTA2, MTA3. MTA1 was the first found member and later reported to be widely expressed in various cancers, including breast cancer, esophageal carcinomas, and gastrointestinal carcinomas. MTA2 has high homology with MTA1 in the protein instruction. Thus, MTA2 may play an important role in the growth of tumor. However, the effects and mechanism of MTA2 in breast cancer is unknown, we further investigate the role of the molecular mechanisms of MTA2 in breast cancer to provide new ideas for breast cancer targeted therapy.Purpose Detect expression of MTA2 in the breast cancer and adjacent tissue. Knocking down MTA2 in breast cancer cells by RNAi technology to explore the effect of MTA2 on cell proliferation, cell cycle, migration ability and the subcutaneous tumor growth in animals, to clarify the mechanism of MTA2 in the development and progression of breast cancer and provide the theoretical basis for MTA2 as a biological therapeutic target on breast cancer.Methods Realtime-PCR was performed to detect the MTA2 mRNA expression; breast cell lines that stably expressed the specific shRNA against MTA2 to knock down the level of MTA2 was constructed; Western immunoblot analysis was performed to detect various gene expression in cell line; Cell Counting kit 8 (CCK-8) was used to evaluate cell proliferation in vitro. Cell cycle and in vitro was analyzed by flow cytometry (FCM). Transwell and wound heal assay was used to detected the migration ability. Nude mouse xenograft assay were used to assess the tumorigenic ability of the stable cells in vivo.Results MTA2 mRNA levels were significantly higher in breast carcinoma than the adjacent tissues; We successfully constructed a stable breast cancer cell lines with knocking out MTA2; Knock down MTA2 can significantly inhibit the proliferation, colony formation, cell cycle progression, migration ability of breast cancer cell; Breast cancer cell lines tumorigenicity in nude mice was significantly less in MTA2 shRNA group than the control group; The ERK/MAPK signal pathway proteins P-MEK, P-ERK, P-MAPK and P-JNK were reduced when MTA2 was knocked out.Conclusion Overexpression of MTA2 in breast cancer can promote cell proliferation, cell cycle progression, cell migration by activating the ERK/MAPK signal pathway and ultimately contributed to the development of breast cancer, so the development of a target molecule for MTA2 is expected to become a new treatment of breast cancer targeted therapy.