Knockin of mutant PIK3CA activates multiple oncogenic pathways
0301 basic medicine
0303 health sciences
Glycogen Synthase Kinase 3 beta
Class I Phosphatidylinositol 3-Kinases
TOR Serine-Threonine Kinases
Mice, Nude
Breast Neoplasms
Oncogenes
3. Good health
Glycogen Synthase Kinase 3
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Cell Line, Tumor
Mutation
Animals
Humans
Gene Knock-In Techniques
Phosphorylation
Colorectal Neoplasms
Extracellular Signal-Regulated MAP Kinases
Mammary Glands, Human
Protein Kinases
Proto-Oncogene Proteins c-akt
DOI:
10.1073/pnas.0813351106
Publication Date:
2009-02-07T05:06:11Z
AUTHORS (18)
ABSTRACT
The phosphatidylinositol 3-kinase subunit PIK3CA is frequently mutated in human cancers. Here we used gene targeting to "knock in" mutations into breast epithelial cells identify new therapeutic targets associated with oncogenic PIK3CA. Mutant knockin were capable of epidermal growth factor and mTOR-independent cell proliferation that was AKT, ERK, GSK3beta phosphorylation. Paradoxically, the inhibitors lithium chloride SB216763 selectively decreased colorectal cancer lines led a decrease target CYCLIN D1. Oral treatment preferentially inhibited nude mouse xenografts HCT-116 colon mutant compared isogenic knockout containing only wild-type Our findings suggest an important effector PIK3CA, lithium, FDA-approved therapy for bipolar disorders, has selective antineoplastic properties against cancers harbor these mutations.
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CITATIONS (142)
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