The Role Of MTORC1/c-myc Loop In The Development Of Breast Cancer

Background: Breast cancer is the main cause of the increase in morbidity and mortality in the global female population,and it seriously threatens the health of women.The underlying mechanism of breast cancer development is closely related to the imbalance of different signal transduction pathways in breast epithelial cells.c-myc,a Myc oncoprotein superfamily,is a proto-oncogene that has c-myc disorders in nearly half of human tumors,including breast cancer.Although the current study found that c-myc is overexpressed in breast cancer and promotes the development of breast cancer,the reason of c-myc overexpression in breast cancer remains unclear.m TORC1 is also abnormally activated in many breast cancers and can promote breast cancer growth and metastasis.In the previous study,we found that m TORC1 activated in mouse embryonic fibroblasts(MEFs)up-regulated the expression of c-myc,and can significantly promote the biological behavior of MEFs such as proliferation and migration,Therefore,whether there is such a relationship in breast cancer remains to be further studied.Objective: To investigate the relationship between c-myc and m TORC1 in breast cancer and its role in breast cancer.Methods: We collected 20 cases of breast cancer clinical samples,extract tissue proteins,Western blot detection c-myc and p S6(effector of m TORC1)protein level expression.The m TORC1 activity in breast cancer T-47 D and MDA-MB-231 cell lines was then inhibited by m TORC1-specific inhibitors of rapamycin and si RNA(sim TOR,si Raptor,si Rictor)and m TORC1 knockdown was established with a lentivirus Low-cell lines,the expression of c-myc protein was detected by western blot and the expression of c-myc m RNA was detected by q RT-PCR.the same method we used c-myc specific inhibitor 10074G5 and small si RNA interference(sic-myc)inhibition c-myc activity in breast cancer T-47 D and MDA-MB-231 cell lines,c-myc knockdown cell line was established by lentivirus(shc-myc),and p-S6 protein level was detected by western blot.The effect of c-myc on the biological behavior of breast cancer cells was examined by MTT,clonogenic assay and scratch assay.The relationship between c-myc and the prognosis of breast cancer was analyzed by online database with the Kaplan Meier Plotter.Results: The expression of c-myc was decreased after inhibition of m TORC1 activity in breast cancer T-47 D and MDA-MB-231 cell lines;m TORC1 activity was also decreased when c-myc expression was inhibited;c-myc was highly expressed Breast cancer cell proliferation,migration and cloning formation;m TORC1 inhibitor rapamycin and c-myc inhibitor 10074G5 combination can significantly inhibit breast cancer cell proliferation.Conclusion:(1)Overexpression of m TORC1 up-regulates the expression of c-myc and promotes the proliferation,colony formation and migration of breast cancer cells.(2)There is a loop mechanism between m TORC1 and c-myc,activated m TORC1 is also activated by c-myc while up-regulating c-myc.(3)rapamycin and c-myc inhibitor10074G5 can inhibit the growth of breast cancer cells,providing a new strategy for the treatment of breast cancer.