Epidermal Growth Factor Receptor Expression Escapes Androgen Regulation in Prostate Cancer: A Potential Molecular Switch for Tumor Growth

Androgen deprivation therapy reduces prostate cancer (PCa) tumor growth; however, disease relapse often ensues independently of androgen stimulation, producing androgen refractory tumors with increased invasion, proliferation, and malignancy. Androgens down-regulate epidermal growth factor receptor (EGFR) in normal prostate but not in PCa. Thus, loss of EGFR regulation and altered signaling may, in part, explain the transition of prostate tumors from androgen-dependent to androgen-independent. Studies in animal models, PCa cell lines, and tumor specimens suggest that androgens modulate prostate growth and function via mechanisms that involve “cross-talk” between androgen receptor (AR) and growth factor receptors signaling pathways.

“We reviewed the literature from mid 1980s through 2009 to assess the relationship between androgens and EGFR function in modulating growth of normal and PCa and found the loss of androgen regulation of EGFR in PCa may be responsible for increased tumor growth, invasion and metastasis with important implications on the clinical management of prostate cancer,” said Abdulmaged M. Traish, MBA, PhD, a professor of biochemistry and urology at BUSM, whose paper appears in the current issue of British Journal of Cancer. According to Traish, the loss of regulation of EGFR expression by androgens in PCa represents an important pathway in cellular growth, invasion and metastasis. “Better understanding of this regulation may represent a target for therapeutic management of PCa,” he added.