Adenovirus-mediated p16^INK4 gene transfer significantly suppresses human breast cancer growth

Abstract

The p16^INK4 tumor suppressor gene encodes a protein that inhibits cyclin-dependent kinase 4, and its homologous deletion is common in human breast cancer. p16^INK4 gene transfer has been reported to be efficacious in inducing growth inhibition of various human tumors such as brain, lung, prostate, and esophageal cancers. However, the efficiency of the p16^INK4 gene with regard to growth inhibition of human breast cancer has not been studied extensively. To examine its tumor-suppressive function and its potential in breast cancer gene therapy, the wild-type p16^INK4 gene was expressed in an adenovirus-mediated gene delivery system and introduced into breast cancer cell lines that do not express p16^INK4 protein. Expression of the introduced p16^INK4 blocked tumor cell entry into the S phase of the cell cycle, induced tumor cell apoptosis, and inhibited tumor cell proliferation both in vitro and in vivo. These results strongly suggest that p16^INK4 is a tumor suppressor gene and suggest that it has potential utility in breast cancer gene therapy.