Transforming growth factor-beta differentially inhibits epithelial ovarian carcinoma cells from primary and metastatic isolates without up-regulation of p21WAF1.
BACKGROUND: Transforming growth factor-beta (TGF-beta) is known to inhibit primary epithelial ovarian carcinoma cells. The mechanism by which this inhibitory response is achieved is poorly understood. Furthermore, whether this response is consistent in cells from metastatic sites compared with the primary site cells is unknown. The authors wanted to determine whether TGF-beta differentially inhibited ovarian carcinoma cells from primary tumor sites compared with metastatic sites and to establish whether this response was associated with up-regulation of p21WAF1 or overexpression of p53. METHODS: Tumor cells were purified from primary and metastatic sites in five patients with advanced epithelial ovarian carcinoma. TGF-beta effect at concentrations of 10, 1, and 0.1 ng/mL was determined by tritiated thymidine incorporation assay. Expression of p21WAF1 was determined by Northern and slot blot analysis. p53 was detected by immunocytochemistry. RESULTS: Metastatic tumor isolates were more responsive to the inhibitory effect of TGF-beta compared with their corresponding primary tumor isolates at 0.1 ng/mL. Increasing TGF-beta concentration conferred no additional inhibitory effect on the metastatic isolates; however, a dose-related phenomenon was observed in primary tumor isolates. p21WAF1 mRNA was up-regulated in only 2 of 10 primary and metastatic isolates. There was no correlation between TGF-beta responsiveness, p21WAF1 up-regulation, and p53 overexpression. CONCLUSIONS: Differential inhibition was observed between primary and metastatic tumor isolates. p21WAF1 up-regulation and p53 overexpression were not major modulators in TGF-beta regulation of primary and metastatic tumor growth in early passaged ovarian carcinoma cells.
Hurteau, JA; Allison, B; Sutton, GP; Moore, DH; Look, KY; Hurd, W; Bigsby, RM
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