An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice

KM Kinross; KG Montgomery; M Kleinschmidt; P Waring; I Ivetac; A Tikoo; M Saad; L Hare; V Roh; T Mantamadiotis; KE Sheppard; GL Ryland; IG Campbell; KL Gorringe; JG Christensen; C Cullinane; RJ Hicks; RB Pearson; RW Johnstone; GA McArthur; WA Phillips

Journal article

An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice

KM Kinross, KG Montgomery, M Kleinschmidt, P Waring, I Ivetac, A Tikoo, M Saad, L Hare, V Roh, T Mantamadiotis, KE Sheppard, GL Ryland, IG Campbell, KL Gorringe, JG Christensen, C Cullinane, RJ Hicks, RB Pearson, RW Johnstone, GA McArthur Show all

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2012

DOI: 10.1172/JCI59309

Abstract

Mutations in the gene encoding the p110α subunit of PI3K (PIK3CA) that result in enhanced PI3K activity are frequently observed in human cancers. To better understand the role of mutant PIK3CA in the initiation or progression of tumorigenesis, we generated mice in which a PIK3CA mutation commonly detected in human cancers (the H1047R mutation) could be conditionally knocked into the endogenous Pik3ca locus. Activation of this mutation in the mouse ovary revealed that alone, Pik3ca H1047R induced premalignant hyperplasia of the ovarian surface epithelium but no tumors. Concomitantly, we analyzed several human ovarian cancers and found PIK3CA mutations coexistent with KRAS and/or PTEN mutation..

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University of Melbourne Researchers

Theo Mantamadiotis Author

Karen Sheppard Author

Georgina L Ryland Author

Ian Campbell Author

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Grants

Awarded by NHMRC

Awarded by Association of International Cancer Research

Funding Acknowledgements

We thank Kerry Ardley for animal experiments and the Peter Mac core histology and pathology facilities. This work was supported by the NHMRC (grant no. 628620 to W.A. Phillips and no. 566876 to G.A. McArthur and R.B. Pearson); the Association of International Cancer Research (no. 10-0052 to W.A. Phillips); Pfizer (grant to G.A. McArthur and R.J. Hicks); the Cancer Council Victoria and the Victorian Cancer Agency (grants to R.W. Johnstone); and the Victorian Breast Cancer Research Consortium, Australia (to I.G. Campbell and K.L. Gorringe). Researchers were funded by a Sir Edward Weary Dunlop Fellowship, Cancer Council of Victoria (to G.A. McArthur); research fellowships from the NHMRC (to R.B. Pearson and R.W. Johnstone); Cure Cancer Australia Foundation and Cancer Australia (to I. Ivetac); the Egyptian government and NHMRC (to M. Saad); Australian Postgraduate Research Awards (to L. Hare and G.L. Ryland); and the Swiss National Science Foundation (to V. Roh).