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Dissection of signaling pathways in fourteen breast cancer cell lines using reverse-phase protein lysate microarray.

Abstract：

:Signal transduction pathways play a crucial role in breast cancer development, progression, and response to different therapies. A major problem in breast cancer therapy is the heterogeneity among different tumor types and cell lines commonly used in preclinical studies. To characterize the signaling pathways of some of the commonly used breast cancer cell lines and dissect the relationship among a number of pathways and some key genetic and molecular events in breast cancer development, such as p53 mutation, ErbB2 expression, and estrogen receptor (ER)/progesterone receptor (PR) status, we performed pathway profiling of 14 breast cancer cell lines by measuring the expression and phosphorylation status of 40 different cell signaling proteins with 53 specific antibodies using a protein lysate array. Cluster analysis of the expression data showed that there was close clustering of phosphatidylinositol 3-kinase, Akt, mammalian target of rapamycin (mTOR), Src, and platelet-derived growth factor receptor beta (PDGFRbeta) in all of the cell lines. The most differentially expressed proteins between ER- and PR-positive and ER- and PR-negative breast cells were mTOR, Akt (pThr308), PDGFRbeta, PDGFRbeta (pTyr751), panSrc, Akt (pSer473), insulin-like growth factor-binding protein 5 (IGFBP5), Src (pTyr418), mTOR (pSer2448), and IGFBP2. Many apoptotic proteins, such as apoptosis-inducing factor, IGFBP3, bad, bax, and cleaved caspase 9, were overexpressed in mutant p53-carrying breast cancer cells. Hexokinase isoenzyme 1, ND2, and c-kit were the most differentially expressed proteins in high and low ErbB2-expressing breast cancer cells. This study demonstrated that ER/PR status, ErbB2 expression, and p53 status are major molecules that impact downstream signaling pathways.

journal_name

Technol Cancer Res Treat

journal_title

Technology in cancer research & treatment

authors

Akkiprik M,Nicorici D,Cogdell D,Jia YJ,Hategan A,Tabus I,Yli-Harja O,Y D,Sahin A,Zhang W

doi

10.1177/153303460600500601

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

543-51

issue

eissn

1533-0346

issn

1533-0338

pii

d=3025&c=4218&p=15389&do=detail

journal_volume

pub_type

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Dissection of signaling pathways in fourteen breast cancer cell lines using reverse-phase protein lysate microarray.