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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Lauring J,Cosgrove DP,Fontana S,Gustin JP,Konishi H,Abukhdeir AM,Garay JP,Mohseni M,Wang GM,Higgins MJ,Gorkin D,Reis M,Vogelstein B,Polyak K,Cowherd M,Buckhaults PJ,Park BHdoi
10.1038/onc.2009.516subject
Has Abstractpub_date
2010-04-22 00:00:00pages
2337-45issue
16eissn
0950-9232issn
1476-5594pii
onc2009516journal_volume
29pub_type
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