title: Relationships between progesterone receptor isoforms and the HER/ErbB receptors and ligands network in 299 primary breast cancers.
abstract: BACKGROUND
  The effects of progesterone are mediated by 2 progesterone receptors (PR), PR-A and PR-B. Recently, several lines of evidence have suggested that reduced PR expression may result from hyperactivity in the signaling cascade generated by the HER/ErbB family. The aim of this study was to analyze the relationships between PR isoforms and the network of the HER/ErbB receptors and ligands in breast cancer.
  
  
  METHODS
  299 breast cancer samples from patients operated in our institute for locoregional disease between May 1989 and December 1991 were included. The mRNA expression of total PR-A+B isoforms and PR-B isoform were quantified by real time quantitative RT-PCR using TaqMan® probes.
  
  
  RESULTS
  mRNA levels of the PR isoforms positively correlated with protein levels of estradiol receptors (ER) and PR. The PR isoforms mRNA levels were inversely correlated with clinicopathological markers of tumor aggressiveness, such as SBR grading and lymph node involvement. The PR isoforms positively correlated with the mRNA levels of HER/ErbB receptors and ligands associated with a more differentiated phenotype (HER3, HER4, EGF, AREG, NRG3 and NRG4) while they correlated negatively with those associated with aggressiveness (EGFR, TGFa, HB-EGF, EREG, and NRG2).
  
  
  CONCLUSIONS
  Our results demonstrate the existence of strong correlations between mRNA levels of the PR isoforms, protein levels of hormone receptors, HER/ErbB receptors and ligands network, and thus suggest that crosstalks between PR and the HER family are a hallmark of breast cancer growth.
authors.affiliation: Département de Sénologie, Centre Oscar Lambret, Lille - France.
authors.forename: Clothilde
authors.initials: C
authors.lastname: Lindet
authors.forename: Françoise
authors.initials: F
authors.lastname: Révillion
authors.forename: Valérie
authors.initials: V
authors.lastname: Lhotellier
authors.forename: Louis
authors.initials: L
authors.lastname: Hornez
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Peyrat
authors.forename: Jacques
authors.initials: J
authors.lastname: Bonneterre
mesh_terms: D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D005260:Female; D006801:Humans; D008024:Ligands; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B