Human Gene Set: DOANE_RESPONSE_TO_ANDROGEN_DN


Standard name DOANE_RESPONSE_TO_ANDROGEN_DN
Systematic name M12816
Brief description Genes down-regulated in MDA-MB-453 cells (class A ER(-) [GeneID=2099] breast cancer) after exposure to the androgen R1881 [PubChem=13766].
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16491124   Authors: Doane AS,Danso M,Lal P,Donaton M,Zhang L,Hudis C,Gerald WL
Exact source Table 3S: Fold Change < 1
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced


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