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Comparison of phosphatidylinositol-3-kinase signalling within a panel of human colorectal cancer cell lines with mutant or wild-type PIK3CA
Authors:Morrow Christopher J  Gray Alexander  Dive Caroline
Affiliation:Cellular and Molecular Pharmacology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester M20 4BX, United Kingdom.
Abstract:
Recent studies have identified conserved missense mutations in PIK3CA, the gene encoding the catalytic phosphatidylinositol-3-kinase subunit p110alpha, in a variety of human cancers. Further investigation demonstrated that PIK3CA mutations lead to increased basal phosphatidylinositol-3-kinase activity, promoting cell growth and invasion [Samuels, Y., Diaz, L.A., Jr., Schmidt-Kittler, O., Cummins, J.M., Delong, L., Cheong, I., Rago, C., Huso, D.L., Lengauer, C., Kinzler, K.W., Vogelstein, B. and Velculescu, V.E. (2005) Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7, 561-573]. A panel of commonly used colorectal cancer cell lines was screened for these PIK3CA mutations. Constitutive and IGF-1-stimulated phosphatidylinositol-3-kinase activity, signal response and duration were assessed. In the assays used no differences distinguished cells carrying PIK3CA mutations indicating that these mutations did not significantly alter growth factor stimulated or steady state phosphatidylinositol-3-kinase activity in normal cell culture conditions.
Keywords:PI3-K, phosphatidylinositol-3-kinase   IGF-1, insulin-like growth factor1   RTK, receptor tyrosine kinase   PtdIns(4,5)P2, phosphatidylinositol(4,5)bisphosphate   PtdIns(3,4,5)P3, phosphatidylinositol(3,4,5)triphosphate   PKB, protein kinase B   PTEN, phosphatase and tensin homologue deleted on chromosome 10   MIN, micro-satellite instability   CRC, colorectal cancer   S.E.M., standard error of the mean
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