A gene transcription signature associated with hormone independence in a subset of both breast and prostate cancers

Background: The development of resistance to hormone therapy in both breast and prostate cancers is attributed to tens of thousands of patient deaths every year. Results: From analyses of global gene expression profile data, a nonrandom amount of overlap was observed between the set of genes associated with estrogen receptor negative (ER-), hormone independent breast cancer and the set of genes associated with androgen independent (AI) prostate cancer. A set of 81 genes was identified that were differentially expressed between ER and ER+ clinical breast tumors and breast cancer cell lines and that showed concordant expression in AI versus AS ( androgen sensitive) prostate cell lines. This common gene signature of hormone independence was used to identify a subset of clinically localized primary prostate tumors that shared extensive similarities in gene transcription with both ER-breast and AI prostate cell lines and that tended to show concurrent deactivation of the androgen signaling pathway. Both ER-breast and AI prostate cell lines were significantly enriched for transcriptional targets of signaling via epidermal growth factor receptor (EGFR). Conclusion: This study indicates that the growth- and survival- promoting functions of hormone receptors can be bypassed in a subset of both breast and prostate cancers by the same growth factor signaling pathways, which holds implications for the use of targeted therapy regimens.