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Endocrine-Related Cancer 13 (4) 1109-1120    DOI: 10.1677/erc.1.01120
Copyright © 2006 by the Society for Endocrinology.
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Identification of novel genes that co-cluster with estrogen receptor alpha in breast tumor biopsy specimens, using a large-scale real-time reverse transcription-PCR approach

S Tozlu1,2, I Girault1,2, S Vacher1,2, J Vendrell3, C Andrieu1,2, F Spyratos1,2, P Cohen3, R Lidereau1,2 and I Bieche1,2

1 Centre René Huguenin, FNCLCC, St-Cloud F-92210, France
2 INSERM, U735, St-Cloud F-92210, France
3 CNRS UMR 5160, Faculté de Pharmacie, Centre de Biotechnologie et de Pharmacologie pour la Santé, Montpellier, France

(Requests for offprints should be addressed to I Bieche, Centre René Huguenin, FNCLCC, St-Cloud F-92210, France; Email: i.bieche{at}stcloud-huguenin.org)

The estrogen receptor alpha (ER{alpha}) plays a critical role in the pathogenesis and clinical behavior of breast cancer. To obtain further insights into the molecular basis of estrogen-dependent forms of this malignancy, we used real-time quantitative reverse transcription (RT)-PCR to compare the mRNA expression of 560 selected genes in ER{alpha}-positive and ER{alpha}-negative breast tumors. Fifty-one (9.1%) of the 560 genes were significantly upregulated in ER{alpha}-positive breast tumors compared with ER{alpha}-negative breast tumors. In addition to well-known ER{alpha}-induced genes (PGR, TFF1/PS2, BCL2, ERBB4, CCND1, etc.) and genes recently identified by cDNA microarray-based approaches (GATA3, TFF3, MYB, STC2, HPN/HEPSIN, FOXA1, XBP1, SLC39A6/LIV-1, etc.), an appreciable number of novel genes were identified, many of, which were weakly expressed. This validates the use of large-scale real-time RT-PCR as a method complementary to cDNA microarrays for molecular tumor profiling. Most of the new genes identified here encoded secreted proteins (SEMA3B and CLU), growth factors (BDNF, FGF2 and EGF), growth factor receptors (IL6ST, PTPRT, RET, VEGFR1 and FGFR2) or metabolic enzymes (CYP2B6, CA12, ACADSB, NAT1, LRBA, SLC7A2 and SULT2B1). Importantly, we also identified a large number of genes encoding proteins with either pro-apoptotic (PUMA, NOXA and TATP73) or anti-apoptotic properties (BCL2, DNTP73 and TRAILR3). Surprisingly, only a small proportion of the 51 genes identified in breast tumor biopsy specimens were confirmed to be ER{alpha}-regulated and/or E2-regulated in vitro (cultured cell lines). Therefore, this study identified a limited number of genes and signaling pathways, which better delineate the role of ER{alpha} in breast cancer. Some of the genes identified here could be useful for diagnosis or for predicting endocrine responsiveness, and could form the basis for novel therapeutic strategies.




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