Tumor Suppressor Activity of the EphB2 Receptor in Prostate Cancer

摘要

Mutations have been recently identified in the EphB2 receptor gene in prostate cancer suggesting that EphB2, a member of the large Eph receptor tyrosine kinase family, is a tumor suppressor in prostate cancer. Consistent with a tumor suppressor activity, we found that EphB2 is more highly expressed in non-transformed BPH-1 prostate epithelial cells than in several prostate cancer cell lines. Furthermore, EphB2 expression was rapidly lost in stably transfected DU145 prostate cancer cells, suggesting that EphB2 has detrimental effects on cell growth and/or survival. We have also uncovered a novel tumor suppressor pathway downstream of the related EphA2 receptor in prostate cancer cells. We found that EphA2 inhibits the AktmTOR pathway, a pathway well known to play a critical role in prostate cancer pathogenesis, and are investigating the mechanisms underlying this important function of EphA2. The tumor suppressor activities of the Eph receptors in prostate cancer represent an important area of investigation that will help understand the pathogenesis of this disease and guide the design of novel diagnostic and therapeutic strategies.