title: Distinct genes related to drug response identified in ER positive and ER negative breast cancer cell lines.
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.
authors: Precision Therapeutics, Inc., Pittsburgh, Pennsylvania, United States of America.
authors: Kui
authors: K
authors: Shen
authors: Shara D
authors: SD
authors: Rice
authors: David A
authors: DA
authors: Gingrich
authors: Dakun
authors: D
authors: Wang
authors: Zhibao
authors: Z
authors: Mi
authors: Chunqiao
authors: C
authors: Tian
authors: Zhenyu
authors: Z
authors: Ding
authors: Stacey L
authors: SL
authors: Brower
authors: Paul R
authors: PR
authors: Ervin
authors: Michael J
authors: MJ
authors: Gabrin
authors: George
authors: G
authors: Tseng
authors: Nan
authors: N
authors: Song
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D015201:Meta-Analysis as Topic; D025341:Principal Component Analysis; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D011960:Receptors, Estrogen