| Abstract: |
Results of recent studies indicate that cultured, androgen-independent prostatic carcinoma cells synthesize and secrete transforming growth factor a, which interacts with epidermal growth factor receptors (EGFRs) to promote autonomous growth. In the present study, we evaluated the expression and constitutive activation of EGFRs in normal prostatic epithelial cells and the androgen-independent prostatic carcinoma cell lines PC3 and DU145. Our studies showed that cultured normal epithelial cells and androgen-independent prostatic carcinoma cells actively synthesize and exhibit constitutive phosphorylation of the Mr 170,000 EGFR. The addition of monoclonal anti-EGFR reduced receptor phosphorylation and significantly inhibited the proliferation of prostatic tumor cells. The observed reduction in EGFR phosphorylation could be partially attributed to an antibody-induced decrease in the expression of metabolically labeled EGFR. Results of further studies showed that anti-EGFR enhanced the sensitivity of PC3 cells to the cytotoxic and cytostatic effects of tumor necrosis factor a. These studies demonstrate that constitutive activation of EGFR in androgen-independent prostatic carcinoma plays a functional role in the regulation of cellular proliferation in vitro. In addition, the enhanced sensitivity of prostatic carcinoma cells to tumor necrosis factor a in the presence of anti-EGFR provides a rationale for the further investigation of combination therapy in the treatment of disseminated, androgen-independent disease. © 1992, American Association for Cancer Research. All rights reserved. |
| Keywords: |
epidermal growth factor; controlled study; human cell; androgen; cell division; gene expression; cell growth; epidermal growth factor receptor; mitogenesis; receptor, epidermal growth factor; cytotoxicity; tumor cells, cultured; phosphorylation; monoclonal antibody; prostatic neoplasms; antibodies, monoclonal; tumor necrosis factor alpha; isotope labeling; prostate epithelium; immunoprecipitation; drug sensitivity; carcinoma cell; prostate carcinoma; polyacrylamide gel electrophoresis; electrophoresis, polyacrylamide gel; tumor necrosis factor; growth inhibition; human; male; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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