RRC ID 42899
Author Hollestelle A, Elstrodt F, Nagel JH, Kallemeijn WW, Schutte M.
Title Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines.
Journal Mol Cancer Res
Abstract Constitutive activation of the phosphatidylinositol-3-OH kinase (PI3K) and RAS signaling pathways are important events in tumor formation. This is illustrated by the frequent genetic alteration of several key players from these pathways in a wide variety of human cancers. Here, we report a detailed sequence analysis of the PTEN, PIK3CA, KRAS, HRAS, NRAS, and BRAF genes in a collection of 40 human breast cancer cell lines. We identified a surprisingly large proportion of cell lines with mutations in the PI3K or RAS pathways (54% and 25%, respectively), with mutants for each of the six genes. The PIK3CA, KRAS, and BRAF mutation spectra of the breast cancer cell lines were similar to those of colorectal cancers. Unlike in colorectal cancers, however, mutational activation of the PI3K pathway was mutually exclusive with mutational activation of the RAS pathway in all but 1 of 30 mutant breast cancer cell lines (P = 0.001). These results suggest that there is a fine distinction between the signaling activators and downstream effectors of the oncogenic PI3K and RAS pathways in breast epithelium and those in other tissues.
Volume 5(2)
Pages 195-201
Published 2007-2
DOI 10.1158/1541-7786.MCR-06-0263
PII 5/2/195
PMID 17314276
MeSH Breast Neoplasms / genetics* Breast Neoplasms / metabolism Cell Line, Tumor DNA Mutational Analysis Humans Mutation* Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Polymerase Chain Reaction Signal Transduction* ras Proteins / genetics* ras Proteins / metabolism
IF 4.484
Times Cited 218
Human and Animal Cells