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Distinct genes related to drug response identified in ER positive and ER negative breast cancer cell lines

Shen, K and Rice, SD and Gingrich, DA and Wang, D and Mi, Z and Tian, C and Ding, Z and Brower, SL and Ervin, PR and Gabrin, MJ and Tseng, G and Song, N (2012) Distinct genes related to drug response identified in ER positive and ER negative breast cancer cell lines. PLoS ONE, 7 (7).

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Abstract

Breast cancer patients have different responses to chemotherapeutic treatments. Genes associated with drug response can provide insight to understand the mechanisms of drug resistance, identify promising therapeutic opportunities, and facilitate personalized treatment. Estrogen receptor (ER) positive and ER negative breast cancer have distinct clinical behavior and molecular properties. However, to date, few studies have rigorously assessed drug response genes in them. In this study, our goal was to systematically identify genes associated with multidrug response in ER positive and ER negative breast cancer cell lines. We tested 27 human breast cell lines for response to seven chemotherapeutic agents (cyclophosphamide, docetaxel, doxorubicin, epirubicin, fluorouracil, gemcitabine, and paclitaxel). We integrated publicly available gene expression profiles of these cell lines with their in vitro drug response patterns, then applied meta-analysis to identify genes related to multidrug response in ER positive and ER negative cells separately. One hundred eighty-eight genes were identified as related to multidrug response in ER positive and 32 genes in ER negative breast cell lines. Of these, only three genes (DBI, TOP2A, and PMVK) were common to both cell types. TOP2A was positively associated with drug response, and DBI was negatively associated with drug response. Interestingly, PMVK was positively associated with drug response in ER positive cells and negatively in ER negative cells. Functional analysis showed that while cell cycle affects drug response in both ER positive and negative cells, most biological processes that are involved in drug response are distinct. A number of signaling pathways that are uniquely enriched in ER positive cells have complex cross talk with ER signaling, while in ER negative cells, enriched pathways are related to metabolic functions. Taken together, our analysis indicates that distinct mechanisms are involved in multidrug response in ER positive and ER negative breast cells. © 2012 Shen et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Shen, K
Rice, SD
Gingrich, DA
Wang, D
Mi, Z
Tian, C
Ding, Z
Brower, SL
Ervin, PR
Gabrin, MJ
Tseng, Gctseng@pitt.eduCTSENG
Song, N
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorKatz, EladUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 16 July 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0040900
Schools and Programs: School of Public Health > Biostatistics
Refereed: Yes
Other ID: NLM PMC3397945
PubMed Central ID: PMC3397945
PubMed ID: 22815861
Date Deposited: 05 Oct 2012 19:08
Last Modified: 10 Jun 2023 11:55
URI: http://d-scholarship.pitt.edu/id/eprint/15588

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