An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen Journal Article
| Authors: | Doane, A. S.; Danso, M.; Lal, P.; Donaton, M.; Zhang, L.; Hudis, C.; Gerald, W. L. |
| Article Title: | An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen |
| Abstract: | Little is known of the underlying biology of estrogen receptor-negative, progesterone receptor-negative (ER(-)/PR(-)) breast cancer (BC), and few targeted therapies are available. Clinical heterogeneity of ER(-)/PR(-) tumors suggests that molecular subsets exist. We performed genome-wide expression analysis of 99 primary BC samples and eight BC cell lines in an effort to reveal distinct subsets, provide insight into their biology and potentially identify new therapeutic targets. We identified a subset of ER(-)/PR(-) tumors with paradoxical expression of genes known to be either direct targets of ER, responsive to estrogen, or typically expressed in ER(+) BC. Differentially expressed genes included SPDEF, FOXA1, XBP1, CYB5, TFF3, NAT1, APOD, ALCAM and AR (P<0.001). A classification model based on the expression signature of this tumor class identified molecularly similar BCs in an independent human BC data set and among BC cell lines (MDA-MB-453). This cell line demonstrated a proliferative response to androgen in an androgen receptor-dependent and ER-independent manner. In addition, the androgen-induced transcriptional program of MDA-MB-453 significantly overlapped the molecular signature of the unique ER(-)/PR(-) subclass of human tumors. This subset of BCs, characterized by a hormonally regulated transcriptional program and response to androgen, suggests the potential for therapeutic strategies targeting the androgen signaling pathway. © 2006 Nature Publishing Group All rights reserved. |
| Keywords: | immunohistochemistry; human tissue; protein expression; human cell; androgen; phenotype; gene; breast cancer; gene expression; gene expression profiling; transcription, genetic; breast neoplasms; gene expression regulation; transcription regulation; rna, messenger; nucleotide sequence; androgen receptor; receptors, estrogen; estrogen receptor; progesterone receptor; hormonal regulation; unindexed sequence; androgens; nat1 gene; androgen responsive; estrogen receptor-negative; alcam gene; apod gene; ar gene; cyb5 gene; foxa1 gene; spdef gene; tff3 gene; xbp1 gene |
| Journal Title: | Oncogene |
| Volume: | 25 |
| Issue: | 28 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2006-06-29 |
| Start Page: | 3994 |
| End Page: | 4008 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1209415 |
| PUBMED: | 16491124 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 119" - "Export Date: 4 June 2012" - "CODEN: ONCNE" - "Source: Scopus" |
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