Expression of activated PIK3CA in ovarian surface epithelium results in hyperplasia but not tumor formation.
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.
Liang
Shun
S
Center for Research on the Early Detection and Cure of Ovarian Cancer, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Yang
Nuo
N
Pan
Yue
Y
Deng
Shan
S
Lin
Xiaojuan
X
Yang
Xiaojun
X
Katsaros
Dionyssios
D
Roby
Katherine F
KF
Hamilton
Thomas C
TC
Connolly
Denise C
DC
Coukos
George
G
Zhang
Lin
L
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*
D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human