Transcriptome changes induced by docetaxel in human mammary cell lines expressing different levels of ERBB2

Abstract

Abstract. The taxane docetaxel is currently the most effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. The mechanisms of docetaxel resistance are poorly understood. Overexpression of ERBB2 occurs in 15-30% of breast tumors and is associated with chemoresistance to a variety of anticancer drugs. In the present study, we sought to identify genes involved in ERBB2-mediated chemoresistance to docetaxel. We generated SAGE libraries from two human mammary cell lines expressing basal (HB4a) and high (C5.2) levels of ERBB2 before and after intensive exposure to docetaxel and identified potential ERBB2 target genes implicated in a variety of cellular processes including cell proliferation, cell adhesion, apoptosis and cytoskeleton organization. Comparison of the transcriptome of the cell lines before and after docetaxel exposure revealed substantially different expression patterns. Twenty-one differentially expressed genes between HB4a and C5.2 cell lines, before and after docetaxel treatment, were further analyzed by qPCR. The alterations in the expression patterns in HB4a and C5.2 cell lines in response to docetaxel treatment observed by SAGE analysis were confirmed by qPCR for the majority of the genes analyzed. Our study provides a comprehensive view of the expression changes induced in two human mammary cells expressing different levels of ERBB2 in response to docetaxel that could contribute to the elucidation of the mechanisms involved in ERBB2-mediated chemoresistance in breast cancer.

EPA and DHA Fatty Acids Induce a Remodeling of Tumor Vasculature and Potentiate Docetaxel Activity

“…These two effectors are also clinically relevant since their mRNA levels in primary tumors can predict the outcome of metastatic colorectal cancer [35]. In two pre-clinical studies, AREG/EREG were not identified as regulated targets by docetaxel treatment [36,37]. However, AREG expression levels have been associated with disease progression of breast cancer or head and neck squamous cell carcinoma in patients receiving a combination treatment of anti-EGFRs and docetaxel [38,39].…”

In silico analyses identify lncRNAs: WDFY3-AS2, BDNF-AS and AFAP1-AS1 as potential prognostic factors for patients with triple-negative breast tumors

“…Moreover, abnormal SPARC expression has been associated with tumor characteristics such as growth and metastasis in different cancer types [38]. Previous studies from our group evaluating the gene expression profile in breast epithelial cells with the difference in ERBB2 expression before and after treatment with Docetaxel identified differential expression of SPARC as a potential biomarker of chemosensitivity [39,40]. Subsequently, we investigate the potential prognostic value of the SPARC protein using immunohistochemical analysis on tissue-microarrays.…”