The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors.

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.

[1]  D. Roymans,et al.  Phosphatidylinositol 3-kinases in tumor progression. , 2001, European journal of biochemistry.

[2]  H. Chapuis,et al.  A specific function for phosphatidylinositol 3-kinase α (p85α-p110α) in cell survival and for phosphatidylinositol 3-kinase β (p85α-p110β) in de novo DNA synthesis of human colon carcinoma cells , 2000, Oncogene.

[3]  Chen-Yang Shen,et al.  PIK3CA as an oncogene in cervical cancer , 2000, Oncogene.

[4]  Domenico Coppola,et al.  Frequent activation of AKT2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer , 2000, Oncogene.

[5]  B. Vanhaesebroeck,et al.  The PI3K-PDK1 connection: more than just a road to PKB. , 2000, The Biochemical journal.

[6]  M. Waterfield,et al.  Signaling by distinct classes of phosphoinositide 3-kinases. , 1999, Experimental cell research.

[7]  Julian Downward,et al.  Akt/PKB localisation and 3′ phosphoinositide generation at sites of epithelial cell–matrix and cell–cell interaction , 1999, Current Biology.

[8]  L. Cantley,et al.  New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Joe W. Gray,et al.  PIK3CA is implicated as an oncogene in ovarian cancer , 1999, Nature Genetics.

[10]  C. Mitchell,et al.  Increased levels of phosphatidylinositol 3‐kinase activity in colorectal tumors , 1998, Cancer.

[11]  A. Schulz,et al.  An oncogenic fusion product of the phosphatidylinositol 3-kinase p85β subunit and HUMORF8, a putative deubiquitinating enzyme , 1998, Oncogene.

[12]  J. Downward,et al.  Identification and characterization of a new oncogene derived from the regulatory subunit of phosphoinositide 3‐kinase , 1998, The EMBO journal.

[13]  Y. Yazaki,et al.  p85α Gene Generates Three Isoforms of Regulatory Subunit for Phosphatidylinositol 3-Kinase (PI 3-Kinase), p50α, p55α, and p85α, with Different PI 3-Kinase Activity Elevating Responses to Insulin* , 1997, The Journal of Biological Chemistry.

[14]  C. Kahn,et al.  Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain , 1996, Molecular and cellular biology.

[15]  R. Bast,et al.  A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1. , 1994, Human molecular genetics.

[16]  I Gout,et al.  PI 3‐kinase is a dual specificity enzyme: autoregulation by an intrinsic protein‐serine kinase activity. , 1994, The EMBO journal.

[17]  R. Whitehead,et al.  Retention of tissue‐specific phenotype in a panel of colon carcinoma cell lines: Relationship to correlates , 1992 .

[18]  R. Whitehead,et al.  Retention of tissue-specific phenotype in a panel of colon carcinoma cell lines: relationship to clinical correlates. , 1992, Immunology and cell biology.

[19]  F. Walker,et al.  A new gastric carcinoma cell line (LIM1839) derived from a young caucasian male , 1989, International journal of cancer.

[20]  R. Whitehead,et al.  A new colon carcinoma cell line (LIM1863) that grows as organoids with spontaneous differentiation into crypt-like structures in vitro. , 1987, Cancer research.

[21]  R. Whitehead,et al.  A colon cancer cell line (LIM1215) derived from a patient with inherited nonpolyposis colorectal cancer. , 1985, Journal of the National Cancer Institute.