PlK3CA is implicated as an oncogene in ovarian cancer

Laleh Shayesteh, Yiling Lu, Wen Lin Kuo, Russell Baldocchi, Tony Godfrey, Colin Collins, Daniel Pinkel, Bethan Powell, Gordon B. Mills, Joe W. Gray

Research output: Contribution to journalArticle

979 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)99-102
Number of pages4
JournalNature genetics
Volume21
Issue number1
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Shayesteh, L., Lu, Y., Kuo, W. L., Baldocchi, R., Godfrey, T., Collins, C., Pinkel, D., Powell, B., Mills, G. B., & Gray, J. W. (1999). PlK3CA is implicated as an oncogene in ovarian cancer. Nature genetics, 21(1), 99-102. https://doi.org/10.1038/5042