TY - JOUR
T1 - The role of genetic abnormalities of PTEN and the phosphatidylinositol 3-kinase pathway in breast and ovarian tumorigenesis, prognosis, and therapy
AU - Mills, Gordon B.
AU - Lu, Yiling
AU - Fang, Xianjun
AU - Wang, Hongwei
AU - Eder, Astrid
AU - Mao, Muling
AU - Swaby, Ramona
AU - Cheng, Kwai Wa
AU - Stokoe, David
AU - Siminovitch, Kathy
AU - Jaffe, Robert
AU - Gray, Joe
N1 - Funding Information:
Supported by National Institutes of Health grunt nos. R01 CA8271 6 (GBM and KS), P50CA83639 (GBM), and PO1 CA64602 (GBM and DS) Address reprint requests to Gordon B. Mills, MD, Department of Molecular Therapeutics, Division of Cancer Medicine, Box 317, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Bled, Houston, TX 77005. Copyright 0 2001 by W.B. Saunders Company 0093.7754/0i/2805~1612$35.00/0 doi:10.1053/sonc.2001.28554
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1053/sonc.2001.28554
DO - 10.1053/sonc.2001.28554
M3 - Article
C2 - 11706404
AN - SCOPUS:0035168724
SN - 0093-7754
VL - 28
SP - 125
EP - 141
JO - Seminars in Oncology
JF - Seminars in Oncology
IS - 5 SUPPL. 16
ER -