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Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells.

Publication ,  Journal Article
Elbendary, A; Berchuck, A; Davis, P; Havrilesky, L; Bast, RC; Iglehart, JD; Marks, JR
Published in: Cell Growth Differ
December 1994

Transforming growth factor beta (TGF beta) is an important regulator of cellular proliferation. In normal ovarian epithelial cells, TGF beta acts to inhibit growth. However, in ovarian cancer cell lines, this effect is usually lost. Although the regulatory pathway of TGF beta remains unclear, TGF beta-treated cells arrest late in G1. This inhibition appears to involve blocking of the cyclin-dependent kinase phosphorylation of the retinoblastoma protein. Recently, a general inhibitor of cyclin-dependent kinases, CIP1/WAF1/p21, was identified. Expression of CIP1 is positively regulated by binding of wild-type p53 to a consensus response element upstream of the CIP1 gene. Overexpression of the CIP1 protein causes growth suppression, analogous to TGF beta and wild-type p53. We have examined the induction of CIP1 by TGF beta 1 in ovarian cancer cell lines that have been previously characterized for their proliferative response to TGF beta 1. OVCA420, a cell line that is dramatically growth inhibited by TGF beta 1, significantly induced CIP1 expression in response to TGF beta 1. CIP1 induction was accompanied by a decrease in cdk2 kinase activity and cdk2 protein levels. In three other cell lines that respond weakly to TGF beta 1, CIP1 expression was not induced. To determine if TGF beta 1 induction occurs via p53, regulation of p53 RNA and protein was examined. No differences in p53 transcription, steady-state protein level, de novo synthesis, phosphorylation, or subcellular accumulation were noted. Furthermore, TGF beta 1 could not induce transcription from a consensus p53 DNA binding site in the TGF beta 1-response cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Published In

Cell Growth Differ

ISSN

1044-9523

Publication Date

December 1994

Volume

5

Issue

12

Start / End Page

1301 / 1307

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Transfection
  • RNA, Neoplasm
  • Protein Kinase Inhibitors
  • Protamine Kinase
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Humans
 

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Elbendary, A., Berchuck, A., Davis, P., Havrilesky, L., Bast, R. C., Iglehart, J. D., & Marks, J. R. (1994). Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells. Cell Growth Differ, 5(12), 1301–1307.
Elbendary, A., A. Berchuck, P. Davis, L. Havrilesky, R. C. Bast, J. D. Iglehart, and J. R. Marks. “Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells.Cell Growth Differ 5, no. 12 (December 1994): 1301–7.
Elbendary A, Berchuck A, Davis P, Havrilesky L, Bast RC, Iglehart JD, et al. Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells. Cell Growth Differ. 1994 Dec;5(12):1301–7.
Elbendary, A., et al. “Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells.Cell Growth Differ, vol. 5, no. 12, Dec. 1994, pp. 1301–07.
Elbendary A, Berchuck A, Davis P, Havrilesky L, Bast RC, Iglehart JD, Marks JR. Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells. Cell Growth Differ. 1994 Dec;5(12):1301–1307.

Published In

Cell Growth Differ

ISSN

1044-9523

Publication Date

December 1994

Volume

5

Issue

12

Start / End Page

1301 / 1307

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Transfection
  • RNA, Neoplasm
  • Protein Kinase Inhibitors
  • Protamine Kinase
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Humans