@article{32c44625e65c441998bdd3f27bd92068,
title = "Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations",
abstract = "An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. Here, we create a physiologic in vitro model to study the effects of this mutation by using somatic cell gene targeting using the nontumorigenic human breast epithelial cell line, MCF10A. Surprisingly, knock in of E17K into the AKT1 gene had minimal phenotypic consequences and importantly, did not recapitulate the biochemical and growth characteristics seen with somatic cell knock in of PIK3CA hotspot mutations. These results suggest that mutations in critical genes within the PI3-kinase (PI3K) pathway are not functionally equivalent, and that other cooperative genetic events may be necessary to achieve oncogenic PI3K pathway activation in cancers that contain the AKT1 E17K mutation.",
keywords = "Akt1, Breast epithelial cells, Gene targeting, Knock in, Oncogene",
author = "J. Lauring and Cosgrove, {D. P.} and S. Fontana and Gustin, {J. P.} and H. Konishi and Abukhdeir, {A. M.} and Garay, {J. P.} and M. Mohseni and Wang, {G. M.} and Higgins, {M. J.} and D. Gorkin and M. Reis and B. Vogelstein and K. Polyak and M. Cowherd and Buckhaults, {P. J.} and Park, {B. H.}",
note = "Funding Information: JL receives support from the Flight Attendant Medical Research Institute (FAMRI), the V Foundation, and the Maryland Cigarette Restitution Fund, National Institutes of Health Grants CA88843, CA088843-08, The Susan G Komen for the Cure Career Catalyst Grant funded by the trust of Ruby J Nelson in loving memory of Charlotte R Nelson, and the Avon Foundation. DC receives support from National Institutes of Health Grant T32 CA09071-27 and a Young Investigator Award from the American Society of Clinical Oncology Foundation. JP Gustin is a recipient of a Department of Defense Breast Cancer Research Program Predoctoral Fellowship Award W81XWH-06-1-0325. JP Garay is a recipient of a Research Supplement to promote diversity in health-related research. HK is a recipient of a Young Clinical Scientist Award from FAMRI. AMA is supported by a Susan G Komen Foundation Postdoctoral Fellowship Award. GW is a recipient of a Medical Scientist Training Program Fellowship. MM is recipient of a Department of Defense Breast Cancer Predoctoral Training Award (BC083057). BHP acknowledges support from the Avon Foundation, Susan G Komen for the Cure, the Mary Kay Ash Charitable Foundation, the Stewart Trust Fund, National Institutes of Health Grants CA109274 and CA88843, FAMRI, and the Breast Cancer Research Foundation. Funding Information: BHP has received research funding from GlaxoSmithKline in the past, though none of the studies presented here was supported by GlaxoSmithKline. BHP is also a consultant for GlaxoSmithKline and Horizon Discovery Ltd. Under separate licensing agreements between Genzyme Corporation and The Johns Hopkins University, BV is entitled to a share of royalties received by the University on sales of products, though none described in this work. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.",
year = "2010",
month = apr,
doi = "10.1038/onc.2009.516",
language = "English (US)",
volume = "29",
pages = "2337--2345",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "16",
}