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
| Autor: | N C Popescu, Ming Guan, X Zhou, V Tripathi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Cancer Research RHOA Tumor suppressor gene Genetic enhancement Mice Nude Adenoviridae Viral vector Mice Cell Line Tumor Animals Humans Molecular Biology Cell Proliferation biology Cell growth Tumor Suppressor Proteins GTPase-Activating Proteins Prostatic Neoplasms Genetic Therapy Xenograft Model Antitumor Assays Apoptosis Cell culture Androgens biology.protein Cancer research Molecular Medicine DLC1 |
| Zdroj: | Cancer Gene Therapy. 15:371-381 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/cgt.2008.13 |
| Popis: | Our recent study showing highly recurrent loss of function of DLC1 (deleted in liver cancer 1), a tumor suppressor gene in primary prostate carcinoma (PCA), implicates this gene in the pathogenesis of this disease. To evaluate the response of PCA to oncosuppressive activity of DLC1, we examined now the effects of adenoviral vector for human DLC1 transduction into the DLC1-deficient, androgen-independent (AI) and aggressive human PCA cell lines PC-3 and C4-2-B2. Adenovirus-mediated restoration of DLC1 expression inhibited the proliferation, invasiveness and anchorage-independent growth of PC-3 and C4-2-B2 cells in vitro as well as the tumorigenicity of PC-3 cells in nude mice. It also induced cell-cycle arrest, inhibited the activation of RhoA and the formation of actin stress fibers. DLC1 induced apoptosis in C4-2-B2 cells, whereas it did not elicit such an effect in PC-3 cells. The abundance of the antiapoptotic protein Bcl-2 was greater in PC-3 cells than in C4-2-B2 cells, and PC-3 cells were rendered sensitive to DLC1-induced apoptosis by treatment with the Bcl-2 inhibitor HA14-1. These results suggest that adenovirus-mediated DLC1 transfer, alone or together with other agents, such as inhibitors of Bcl-2 or histone deacetylase, might prove effective in the treatment of aggressive, AI-PCA. |
| Databáze: | OpenAIRE |
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