p53‑independent role of MYC mutant T58A in the proliferation and apoptosis of breast cancer cells

Myc proto-oncogene (MYC) is an oncoprotein that promotes proliferation and apoptosis. MYC mutations frequently disrupt the apoptotic processes during tumorigenesis. In the present study, the effects of the MYC point mutation T58A on the progression of a cellular tumor antigen p53 (p53)−/− human breast cancer cell line was analyzed, and the mechanism of p53-independent MYC-induced apoptosis was investigated. HCC1937 cells were transfected with mutant (T58A) or wild-type (WT) MYC using lentiviral vectors. The proliferation of transfected cells was evaluated by colony formation and MTT assays, and apoptosis was analyzed by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays. WT MYC was transfected into HCC1937 cells exhibiting p14/p21 silencing through lentivirus-mediated RNA interference. The expression levels of Bim were detected by reverse transcription-quantitative polymerase chain reaction and western blot analyses. Mutant MYC proteins retained the ability to stimulate the proliferation of HCC1937 cells, although they were defective at promoting apoptosis due to a failure to induce the Bcl-2 homology 3 domain-only protein Bim. When p14 was silenced, the effects of mutant MYC on proliferation and apoptosis were weakened. When p21 was silenced, the effects of mutant MYC were strengthened. Breast cancer-derived T58A MYC mutations are unable to activate Bim due to their failure to regulate p14/p21. It was concluded that mutant MYC was more effective compared with WT MYC at promoting the progression of breast cancer.