Cell-type specific responses to chemotherapeutics in breast cancer

ABSTRACT: Recent studies have identified clinical subtypes of breast tumors that arise from different cell types and have different outcomes in response to chemotherapy. Tumors derived from basal epithelium have a poorer prognosis than tumors derived from luminal epithelium. To gain insight into differences underlying this disparity, we treated cell lines derived from basal epithelium (immortalized human mammary epithelial cells) and those derived from luminal epithelium (MCF-7 and ZR-75-1) with two chemotherapeutics commonly used in the treatment of breast cancer. Treatment doses for doxorubicin (DOX) and 5-fluorouracil (5FU) were selected to cause comparable cytotoxicity across all four cell lines. The predominant gene expression in each of the four cell lines was a general stress response, but distinct gene expression patterns were observed depending upon cell type. Both cell types up-regulated DNA damage response genes such as p21waf1, but the response in the luminal cells was much more dramatic and included many p53-regulated genes. Luminal cell lines down-regulated a large number of cell cycle regulators and other genes involved in cellular proliferation, while basal cell lines down-regulated a smaller set of genes, many of which are involved in cellular differentiation. These results were compared to gene expression data from tumor samples collected before and after treatment with DOX or 5FU/mitomycin C. Similarities between the in vitro and in vivo responses validate this model for studying gene expression responses to chemotherapy in these cell types. Understanding cell-type specific responses to chemotherapeutics will help in tailoring treatment to patients based upon tumor characteristics. Keywords = breast cancer Keywords = chemotherapy Keywords = gene expression Keywords = microarray Keywords = stress response Keywords: time-course

ORGANISM(S): Homo sapiens

PROVIDER: GSE763 | GEO | 2004/04/18

SECONDARY ACCESSION(S): PRJNA87715

REPOSITORIES: GEO