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Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells.

Publication ,  Journal Article
Elbendary, AA; Cirisano, FD; Evans, AC; Davis, PL; Iglehart, JD; Marks, JR; Berchuck, A
Published in: Clin Cancer Res
September 1996

In many cell types, p53-mediated growth inhibition is dependent on induction of p21, which is an inhibitor of cyclin-dependent kinases that are required for cell cycle progression. Failure of mutant p53 proteins to transactivate p21 may lead to uncontrolled proliferation. Because many ovarian cancers have mutations in the p53 gene, we examined p21 levels in normal and malignant ovarian epithelial cells to determine whether p21 expression is dependent on wild-type p53. Normal ovarian epithelial cells and two ovarian cancer cell lines with wild-type p53 expressed readily detectable levels of p21, whereas in p53 null and mutant cell lines, expression of p21 was diminished strikingly. A correlation between the status of the p53 gene and p21 expression also was noted in 23 primary epithelial ovarian cancers. Normal levels of p21 RNA were seen in 4/7 (57%) cancers with wild-type p53, whereas 14/16 (88%) cancers with mutant p53 had reduced p21 expression (P < 0.05). In addition, we found that lambda-irradiation of normal and malignant ovarian epithelial cells with wild-type, but not mutant, p53 resulted in induction of p21. These data are suggestive that induction of p21 is a feature of p53-mediated growth inhibition in normal ovarian epithelial cells. Conversely, mutation of the p53 gene in ovarian cancers usually is associated with decreased p21 expression. The lack of an absolute correlation between p21 expression and the status of the p53 gene in ovarian cancers is consistent with other studies that have suggested that p21 may also be regulated by p53-independent pathways.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 1996

Volume

2

Issue

9

Start / End Page

1571 / 1575

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • RNA, Messenger
  • Ovary
  • Oncology & Carcinogenesis
  • Mutation
  • Humans
  • Genes, p53
  • Gene Expression Regulation, Neoplastic
  • Female
  • Epithelial Cells
 

Citation

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MLA
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Elbendary, A. A., Cirisano, F. D., Evans, A. C., Davis, P. L., Iglehart, J. D., Marks, J. R., & Berchuck, A. (1996). Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells. Clin Cancer Res, 2(9), 1571–1575.
Elbendary, A. A., F. D. Cirisano, A. C. Evans, P. L. Davis, J. D. Iglehart, J. R. Marks, and A. Berchuck. “Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells.Clin Cancer Res 2, no. 9 (September 1996): 1571–75.
Elbendary AA, Cirisano FD, Evans AC, Davis PL, Iglehart JD, Marks JR, et al. Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells. Clin Cancer Res. 1996 Sep;2(9):1571–5.
Elbendary, A. A., et al. “Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells.Clin Cancer Res, vol. 2, no. 9, Sept. 1996, pp. 1571–75.
Elbendary AA, Cirisano FD, Evans AC, Davis PL, Iglehart JD, Marks JR, Berchuck A. Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells. Clin Cancer Res. 1996 Sep;2(9):1571–1575.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 1996

Volume

2

Issue

9

Start / End Page

1571 / 1575

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • RNA, Messenger
  • Ovary
  • Oncology & Carcinogenesis
  • Mutation
  • Humans
  • Genes, p53
  • Gene Expression Regulation, Neoplastic
  • Female
  • Epithelial Cells