OCT4B regulates p53 and p16 pathway genes to prevent apoptosis of breast cancer cells.

Octamer-binding transcription factor 4 (OCT4) is a transcription factor with a well-defined role in stem cell pluripotency. Two OCT4 isoforms, OCT4A and OCT4B, tend to be downregulated as normal cells differentiate. However, OCT4, particularly OCT4B, may become reactivated in cancer cells. Despite this observation, the exact function of OCT4B re-expression in cancer is unclear. In the present study, the role of OCT4 in breast cancer cells was determined. In particular, the ability of OCT4 to regulate key genes involved in cellular proliferation and apoptosis, two pathways that are frequently deregulated in cancer, was examined. The cyclin-dependent kinase inhibitor 2A locus encodes p16INK4a and p14ARF, two important cell cycle inhibitors. The tumor suppressor p53 also has well characterized roles in suppressing proliferation and promoting apoptosis. The present study demonstrated, via overexpression and genetic knockdown techniques, that OCT4B regulates the expression of several of these genes and ultimately regulates the rate of apoptosis of MCF-7 breast cancer cells. It was also observed that, while OCT4B and OCT4A regulate one another, it is OCT4B that serves a more prominent role in regulating the transcription of downstream genes. Taken together, the present results suggest that OCT4B is re-expressed in a number of breast cancer cell lines, where it affects both the transcription of cell cycle genes and the rate of apoptosis. These properties of OCT4B may depend on, at least in part, the co-function of OCT4A.