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Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta.

Publication ,  Journal Article
Havrilesky, LJ; Hurteau, JA; Whitaker, RS; Elbendary, A; Wu, S; Rodriguez, GC; Bast, RC; Berchuck, A
Published in: Cancer Res
February 15, 1995

Previously, we found that transforming growth factor beta (TGF-beta) inhibits proliferation of normal human ovarian epithelial cells. In addition, although only 1 of 5 immortalized ovarian cancer cell lines was inhibited, TGF-beta inhibited proliferation of 19 of 20 primary epithelial ovarian cancers. In this study, we examined whether TGF-beta induces apoptosis in normal and malignant ovarian epithelial cells. Among 5 immortalized cell lines, only OVCA 420 is markedly growth inhibited by TGF-beta, and this was the only cell line in which TGF-beta elicited DNA fragmentation characteristic of apoptosis. Induction of apoptosis in OVCA 420 was time and concentration dependent and could be partially inhibited by concurrent treatment with an anti-TGF-beta mAb. Although apoptosis was not seen in normal ovarian epithelial cells (n = 7), [3H]thymidine incorporation was inhibited in all cases [mean = 61.2 +/- 7.2% (SD) of untreated control; P < 0.01]. Similarly, TGF-beta inhibited [3H]thymidine incorporation in all 10 primary ovarian cancers (mean = 40.4 +/- 7.1% of control; P < 0.01), but only 3 of 10 (30%) were found to undergo apoptosis when treated with TGF-beta. There was no relationship between p53 status of the ovarian cancers and the ability of TGF-beta to elicit apoptosis. In conclusion, TGF-beta inhibits proliferation but does not induce apoptosis in normal human ovarian epithelial cells. In contrast, some ovarian cancers that are growth inhibited by TGF-beta also undergo apoptosis. These data are consistent with the hypothesis that malignant cells are more susceptible to apoptosis than their normal nontransformed counterparts.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

February 15, 1995

Volume

55

Issue

4

Start / End Page

944 / 948

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Reference Values
  • Ovary
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Keratins
  • Immunoblotting
  • Humans
  • Genes, p53
 

Citation

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Havrilesky, L. J., Hurteau, J. A., Whitaker, R. S., Elbendary, A., Wu, S., Rodriguez, G. C., … Berchuck, A. (1995). Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta. Cancer Res, 55(4), 944–948.
Havrilesky, L. J., J. A. Hurteau, R. S. Whitaker, A. Elbendary, S. Wu, G. C. Rodriguez, R. C. Bast, and A. Berchuck. “Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta.Cancer Res 55, no. 4 (February 15, 1995): 944–48.
Havrilesky LJ, Hurteau JA, Whitaker RS, Elbendary A, Wu S, Rodriguez GC, et al. Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta. Cancer Res. 1995 Feb 15;55(4):944–8.
Havrilesky, L. J., et al. “Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta.Cancer Res, vol. 55, no. 4, Feb. 1995, pp. 944–48.
Havrilesky LJ, Hurteau JA, Whitaker RS, Elbendary A, Wu S, Rodriguez GC, Bast RC, Berchuck A. Regulation of apoptosis in normal and malignant ovarian epithelial cells by transforming growth factor beta. Cancer Res. 1995 Feb 15;55(4):944–948.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

February 15, 1995

Volume

55

Issue

4

Start / End Page

944 / 948

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Reference Values
  • Ovary
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Keratins
  • Immunoblotting
  • Humans
  • Genes, p53