title: Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation.
abstract: BACKGROUND
  The Phosphatidylinositol 3'-kinase is a key regulator in various cancer-associated signal transduction pathways. Genetic alterations of its catalytic subunit alpha, PIK3CA, have been identified in ovarian cancer. Our in vivo data suggests that PIK3CA activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE) is largely unclear.
  
  
  RESULTS
  Using the Müllerian inhibiting substance type II receptor (MISIIR) promoter, we generated transgenic mice that expressed activated PIK3CA in the Müllerian epithelium. Overexpression of PIK3CA in OSE induced remarkable hyperplasia, but was not able to malignantly transform OSE in vivo. The consistent result was also observed in primary cultured OSEs. Although enforced expression of PIK3CA could not induce OSE anchorage-independent growth, it significantly increased anchorage-independent growth of OSE transformed by mutant K-ras.
  
  
  CONCLUSIONS
  While PIK3CA activation may not be able to initiate OSE transformation, we conclude that activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras.
authors.affiliation: Center for Research on the Early Detection and Cure of Ovarian Cancer, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Shun
authors.initials: S
authors.lastname: Liang
authors.forename: Nuo
authors.initials: N
authors.lastname: Yang
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.forename: Shan
authors.initials: S
authors.lastname: Deng
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Lin
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yang
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Katherine F
authors.initials: KF
authors.lastname: Roby
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Hamilton
authors.forename: Denise C
authors.initials: DC
authors.lastname: Connolly
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D004789:Enzyme Activation; D004848:Epithelium / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D006965:Hyperplasia; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human