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Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells
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Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells
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Journal Article
Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells
2008
Overview
More than 20 different
PIK3CA
gene mutations were identified in breast cancer with different frequencies. Whether these breast cancer associated mutations have similar biological effects is largely unknown. In this study, we established a novel cell model using the lentivirus system to express 10 different
PIK3CA
genes (wild type and mutant) based on the human mammary epithelial cell MCF10A. We found that nine different
PIK3CA
mutants harbor different abilities to promote cell proliferation and EGF independent growth. In addition, most
PIK3CA
mutants (except for the wild type
PIK3CA
, the Q60K and the K111N mutants) had the ability to change the morphogenesis of the MCF10A cell in 3D Matrigel assay. Moreover, different
PIK3CA
mutants have different abilities to promote colony formation and cell invasion. We further observed that most of the
PIK3CA
mutants could activate p-AKT and p-p70-S6K in the absence of EGF stimulation. Finally, LY294002, a PI3K inhibitor, can effectively inhibit cell growth in cell lines with different
PIK3CAs.
Taken together, our results support the notion that different
PIK3CA
mutations differentially contribute to breast cancer transformation, and exploration of the therapeutic application of these mutations will benefit breast cancer patients with the
PIK3CA
mutations.
Publisher
Springer US,Springer,Springer Nature B.V
Subject
Biological and medical sciences
/ Breast Neoplasms - pathology
/ Class I Phosphatidylinositol 3-Kinases
/ Enzyme Inhibitors - pharmacology
/ Epidermal Growth Factor - metabolism
/ Epithelial Cells - metabolism
/ Genes
/ Gynecology. Andrology. Obstetrics
/ Humans
/ Mammary Glands, Human - metabolism
/ Mammary Glands, Human - pathology
/ Medicine
/ Mutation
/ Oncology
/ Phosphatidylinositol 3-Kinases - genetics
/ Phosphatidylinositol 3-Kinases - metabolism
/ Ribosomal Protein S6 Kinases, 70-kDa - metabolism
/ Tumors
