The role of genetic abnormalities of PTEN and the phosphatidylinositol 3-kinase pathway in breast and ovarian tumorigenesis, prognosis, and therapy

Gordon B. Mills, Yiling Lu, Xianjun Fang, Hongwei Wang, Astrid Eder, Muling Mao, Ramona Swaby, Kwai Wa Cheng, David Stokoe, Kathy Siminovitch, Robert Jaffe, Joe Gray

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

Breast and ovarian cancers exhibit similar epidemiologic, genotypic, and phenotypic characteristics. Phosphatidylinositol 3-kinase (P13K) and the PTEN tumor suppressor gene product phosphorylate and dephosphorylate the same 3′ site in the inositol ring of membrane phosphatidylinositols. Germ-line mutations in the PTEN tumor suppressor gene are causative of Cowden's breast cancer predisposition syndrome, and PTEN is frequently mutated in sporadic breast cancers. In contrast, amplification of multiple components of the P13K pathway is a hallmark of serous epithelial ovarian cancers. The resultant activation of the P13K pathway in both breast and ovarian cancers contributes to cell-cycle progression, decreased apoptosis, and increased metastatic capabilities. Strikingly, both ovarian and breast cancer cells are selectively sensitive to pharmacologic and genetic manipulation of the P13K pathway, making molecular therapeutics targeting this pathway particularly attractive approaches for these cancers.

Original languageEnglish (US)
Pages (from-to)125-141
Number of pages17
JournalSeminars in Oncology
Volume28
Issue number5 SUPPL. 16
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Mills, G. B., Lu, Y., Fang, X., Wang, H., Eder, A., Mao, M., Swaby, R., Cheng, K. W., Stokoe, D., Siminovitch, K., Jaffe, R., & Gray, J. (2001). The role of genetic abnormalities of PTEN and the phosphatidylinositol 3-kinase pathway in breast and ovarian tumorigenesis, prognosis, and therapy. Seminars in Oncology, 28(5 SUPPL. 16), 125-141.