title: The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors.
abstract: 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 p85alpha 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 p85alpha is a new oncogene involved in human tumorigenesis.
authors.affiliation: Surgical Oncology Research Laboratory, Peter MacCallum Cancer Institute, Melbourne, Victoria 3002, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Philp
authors.forename: I G
authors.initials: IG
authors.lastname: Campbell
authors.forename: C
authors.initials: C
authors.lastname: Leet
authors.forename: E
authors.initials: E
authors.lastname: Vincan
authors.forename: S P
authors.initials: SP
authors.lastname: Rockman
authors.forename: R H
authors.initials: RH
authors.lastname: Whitehead
authors.forename: R J
authors.initials: RJ
authors.lastname: Thomas
authors.forename: W A
authors.initials: WA
authors.lastname: Phillips
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D003110:Colonic Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009857:Oncogenes / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt