Ovarian cancer is the leading cause of death from gynecological malignancy and the fourth leading cause of cancer death among American women, yet little is known about its molecular aetiology. Studies using comparative genomic hybridization (CGH) have revealed several regions of recurrent, abnormal, DNA sequence copy number that may encode genes involved in the genesis or progression of the disease. One region at 3q26 found to be increased in copy number in approximately 40% of ovarian and others cancers contains PlK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (Pl3-kinase). The association between PlK3CA copy number and Pl3-kinase activity makes PlK3CA a candidate oncogene because a broad range of cancer-related functions have been associated with Pl3- kinase mediated signalling. These include proliferation, glucose transport and catabolism, cell adhesion, apoptosis, RAS signalling and oncogenic transformation. In addition, downstream effectors of Pl3-kinase, AKT1 and AKT2, have been found to be amplified or activated in human tumours, including ovarian cancer. We show here that PlK3CA is frequently increased in copy number in ovarian cancers, that the increased copy number is associated with increased PlK3CA transcription, p110α protein expression and Pl3- kinase activity and that treatment with the Pl3-kinase inhibitor LY294002 decreases proliferation and increases apoptosis. Our observations suggest PlK3CA is an oncogene that has an important role in ovarian cancer.
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