title: From ERα66 to ERα36: a generic method for validating a prognosis marker of breast tumor progression.
abstract: BACKGROUND
  Estrogen receptor alpha36 (ERalpha36), a variant of estrogen receptor alpha (ER) is expressed in about half of breast tumors, independently of the [ER+]/[ER-] status. In vitro, ERalpha36 triggers mitogenic non-genomic signaling and migration ability in response to 17beta-estradiol and tamoxifen. In vivo, highly ERalpha36 expressing tumors are of poor outcome especially as [ER+] tumors are submitted to tamoxifen treatment which, in turn, enhances ERalpha36 expression.
  
  
  RESULTS
  Our study aimed to validate ERalpha36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent proliferative tumor toward an estrogen dispensable metastatic disease. In a retrospective study, we tried to decipher underlying mechanisms of cancer progression by using an original modeling of the relationships between ERalpha36, other estrogen and growth factor receptors and metastatic marker expression. Nonlinear correlation analyses and mutual information computations led to characterize a complex network connecting ERalpha36 to either non-genomic estrogen signaling or to metastatic process.
  
  
  CONCLUSIONS
  This study identifies ERalpha36 expression level as a relevant classifier which should be taken into account for breast tumors clinical characterization and [ER+] tumor treatment orientation, using a generic approach for the rapid, cheap and relevant evaluation of any candidate gene expression as a predictor of a complex biological process.
authors.affiliation: CNRS-Université de Lorraine, UMR 7039, Centre de Recherche en Automatique de Nancy, BP70239, F-54506, Vandœuvre-lès-Nancy, France. clemence.jovenin@univ-lorraine.fr.
authors.forename: Clémence
authors.initials: C
authors.lastname: Chamard-Jovenin
authors.affiliation: EA 3430, Centre Paul Strauss, 3 rue Porte de l'Hôpital, 67000, Strasbourg, France. ajung@strasbourg.unicancer.fr.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Jung
authors.affiliation: CNRS-Université de Lorraine, UMR 7039, Centre de Recherche en Automatique de Nancy, BP70239, F-54506, Vandœuvre-lès-Nancy, France. amand.chesnel@univ-lorraine.fr.
authors.forename: Amand
authors.initials: A
authors.lastname: Chesnel
authors.affiliation: EA 3430, Centre Paul Strauss, 3 rue Porte de l'Hôpital, 67000, Strasbourg, France. jabecassis@strasbourg.unicancer.fr.
authors.forename: Joseph
authors.initials: J
authors.lastname: Abecassis
authors.affiliation: CNRS-Université de Lorraine, UMR 7039, Centre de Recherche en Automatique de Nancy, BP70239, F-54506, Vandœuvre-lès-Nancy, France. stephane.flament@univ-lorraine.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Flament
authors.affiliation: EA 3430, Centre Paul Strauss, 3 rue Porte de l'Hôpital, 67000, Strasbourg, France. sledrappier@strasbourg.unicancer.fr.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ledrappier
authors.affiliation: EA 3430, Centre Paul Strauss, 3 rue Porte de l'Hôpital, 67000, Strasbourg, France. cmacabre@strasbourg.unicancer.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Macabre
authors.affiliation: CNRS-Université de Lorraine, UMR 7039, Centre de Recherche en Automatique de Nancy, BP70239, F-54506, Vandœuvre-lès-Nancy, France. taha.boukhobza@univ-lorraine.fr.
authors.forename: Taha
authors.initials: T
authors.lastname: Boukhobza
authors.affiliation: CNRS-Université de Lorraine, UMR 7039, Centre de Recherche en Automatique de Nancy, BP70239, F-54506, Vandœuvre-lès-Nancy, France. helene.dumond@univ-lorraine.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dumond
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology / Q000379:methods*; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D014644:Genetic Variation; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha