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[Cancer Research 61, 7426-7429, October 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

The Phosphatidylinositol 3'-kinase p85{alpha} Gene Is an Oncogene in Human Ovarian and Colon Tumors1

Amanda J. Philp, Ian G. Campbell, Christine Leet, Elizabeth Vincan, Steven P. Rockman, Robert H. Whitehead2, Robert J. S. Thomas and Wayne A. Phillips3

Surgical Oncology Research Laboratory [A. J. P., C. L., E. V., S. P. R., R. J. S. T., W. A. P.] and Victorian Breast Cancer Research Consortium Cancer Genetics Laboratory [I. G. C.], Peter MacCallum Cancer Institute, Melbourne, Victoria 3002, and Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Melbourne, Victoria 3050 [R. H. W.], Australia

Phosphatidylinositol 3'-kinases (PI3ks) are a family of lipid kinases that play a crucial role in a wide range of important cellular processes associated with malignant behavior including cell growth, migration, and survival. We have used single-strand conformational polymorphism/heteroduplex analysis to demonstrate the presence of somatic mutations in the gene for the p85{alpha} regulatory subunit of PI3k (PIK3R1) in primary human colon and ovarian tumors and cancer cell lines. All of the mutations lead to deletions in the inter-SH2 region of the molecule proximal to the serine608 autoregulatory site. Expression of a mutant protein with a 23 amino acid deletion leads to constitutive activation of PI3k providing the first direct evidence that p85{alpha} is a new oncogene involved in human tumorigenesis.




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