Physiological Levels of Pik3ca(H1047R) Mutation in the Mouse Mammary Gland Results in Ductal Hyperplasia and Formation of ER alpha-Positive Tumors
Anjali Tikoo, Vincent Roh, Karen G Montgomery, Ivan Ivetac, Paul Waring, Rebecca Pelzer, Lauren Hare, Mark Shackleton, Patrick Humbert, Wayne A Phillips
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2012
PIK3CA, the gene coding for the p110α subunit of phosphoinositide 3-kinase, is frequently mutated in a variety of human tumors including breast cancers. To better understand the role of mutant PIK3CA in the initiation and/or progression of breast cancer, we have generated mice with a conditional knock-in of the common activating mutation, Pik3ca(H1047R), into one allele of the endogenous gene in the mammary gland. These mice developed a ductal anaplasia and hyperplasia by 6 weeks of age characterized by multi-layering of the epithelial lining of the mammary ducts and expansion of the luminal progenitor (Lin(-); CD29(lo); CD24(+); CD61(+)) cell population. The Pik3ca(H1047R) expressing mice e..View full abstract
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Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by Association of International Cancer Research
This work was funded by grants from the National Health and Medical Research Council (NHMRC) of Australia (project grant No. 628620) and the Association of International Cancer Research (grant No 10-0052) to WAP. POH was supported by an NHMRC Career Development Award. VR was supported by the Swiss National Science Foundation. II was supported, in part, by the Cure Cancer Australia Foundation and Cancer Australia and LH is the recipient of an Australian Postgraduate Research Award. MS was supported by fellowships from Pfizer Australia and VESKI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.