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).


CONCLUSIONS
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.
Creighton
Chad J
CJ
Department of Medicine, Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX 77030, USA. creighto@bcm.tmc.edu
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006728:Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D015398:Signal Transduction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D006728:Hormones; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D066246:ErbB Receptors