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.

Ramalin‐Mediated Apoptosis Is Enhanced by Autophagy Inhibition in Human Breast Cancer Cells

“…Breast cancer has become the most important cancer in women (Jemal et al , ). In general, ER‐positive cells are present in 60% of patients with breast cancer, and these patients can be treated with anti‐oestrogen therapy; ER‐negative breast cancer is harder to treat (Badve and Nakshatri, ; Shen et al , ). Although there have been many attempts to develop treatments, more effective anticancer agents are still needed for both ER‐positive and ER‐negative breast cancer.…”

“…However, the presence of oestrogen receptors (ERs) is one of the most important general classifications, because ERs play a significant role in several signal transduction pathways of breast cancer cells and affect gene expression and cell characteristics upon exposure to oestrogen. ER‐positive breast cancer is responsive to anti‐oestrogen therapy and leads to a better outcome in general, whereas ER‐negative breast cancer is more aggressive and is usually associated with a poor clinical prognosis (Badve and Nakshatri, ; Shen et al , ). Despite many clinical trials involving numerous agents, the search continues for more effective therapeutic agents targeted to both kinds of breast cancer.…”

A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity

“…Human homologs of ACB1 exhibiting UES (Fig. 5C; 2-0.16-1 ) included: (1) DBI , which is upregulated in hepatocellular carcinoma and lung cancer, and its expression is negatively associated with multidrug resistance in breast cancer [101-103]; (2) ACBD4, which promotes ER-peroxisome associations [98] and is upregulated by a histone deacetylase inhibitor, valproic acid, in a panel of cancer cell lines [99]; and (3) ACBD5, which also promotes ER-peroxisome associations, but its link to cancer is unclear [100]. .…”

Use of ChemoFx® for Identification of Effective Treatments in Epithelial Ovarian Cancer

“…Published studies suggest that ChemoFx represents a novel platform for multigene (microarray) signature development, by associating in vitro assay response data with gene expression profiling data. 9 , 10 , 11 Specifically, a multigene signature developed utilizing the ChemoFx platform has been independently validated, differentiating pathologic complete response from residual disease after neoadjuvant chemotherapy. 9 The ability of ChemoFx to simultaneously assess response to multiple therapies makes this assay especially useful for developing genomic signatures that may predict differential response to therapies.…”