Regulation of growth of normal ovarian epithelial cells andovarian cancer cell lines by transforming growth factor-ß

Abstract

The purpose of this study was to study the role of transforming growth factor-beta in regulation of proliferation of normal and malignant ovarian epithelial cells. We examined production of and responsiveness to transforming growth factor-beta in primary monolayer cultures of epithelial cells from five normal human ovaries and in five ovarian cancer cell lines. In normal ovarian epithelial cells, proliferation always was inhibited by transforming growth factor-beta (greater than 40%) (p less than 0.01). Among the cancer cell lines, proliferation of one was markedly inhibited (greater than 95%) (p less than 0.01), two were only modestly inhibited (15% to 20%) (p less than 0.05), and two were unaffected. In addition, we found that all of the normal ovarian epithelial cells and four of five ovarian cancer cell lines produce transforming growth factor-beta ribonucleic acid and protein. These data suggest that transforming growth factor-beta may act as an autocrine growth inhibitory factor for normal ovarian epithelium in vivo. Because most of the ovarian cancer cell lines are relatively resistant to the growth inhibitory effect of transforming growth factor-beta and because one cell line does not produce transforming growth factor-beta, it is possible that loss of the transforming growth factor-beta pathway may play a role in the development of some ovarian cancers.