Adenovirus-mediated restoration of expression of the tumor suppressor gene DLC1 inhibits the proliferation and tumorigenicity of aggressive, androgen-independent human prostate cancer cell lines: prospects for gene therapy.

摘要: Our recent study showing highly recurrent loss of function DLC1 (deleted in liver cancer 1), a tumor suppressor gene primary prostate carcinoma (PCA), implicates this the pathogenesis disease. To evaluate response PCA to oncosuppressive activity DLC1, we examined now effects adenoviral vector for human transduction into DLC1-deficient, androgen-independent (AI) and aggressive cell lines PC-3 C4-2-B2. Adenovirus-mediated restoration expression inhibited proliferation, invasiveness anchorage-independent growth C4-2-B2 cells vitro as well tumorigenicity nude mice. It also induced cell-cycle arrest, activation RhoA formation actin stress fibers. apoptosis cells, whereas it did not elicit such an effect cells. The abundance antiapoptotic protein Bcl-2 was greater than were rendered sensitive DLC1-induced by treatment with inhibitor HA14-1. These results suggest that adenovirus-mediated transfer, alone or together other agents, inhibitors histone deacetylase, might prove effective aggressive, AI-PCA.