title: RhoB modifies estrogen responses in breast cancer cells by influencing expression of the estrogen receptor.
abstract: BACKGROUND
  RhoB has been reported to exert positive and negative effects on cancer pathophysiology but an understanding of its role in breast cancer remains incomplete. Analysis of data from the Oncomine database showed a positive correlation between RhoB expression and positivity for both estrogen receptor alpha (ERα) and progesterone receptor (PR).
  
  
  METHODS
  This finding was validated by our analysis of a tissue microarray constructed from a cohort of 113 patients and then investigated in human cell models.
  
  
  RESULTS
  We found that RhoB expression in tissue was strongly correlated with ERα and PR expression and inversely correlated with tumor grade, tumor size and count of mitosis. In human breast cancer cell lines, RhoB attenuation was associated with reduced expression of both ERα and PR, whereas elevation of RhoB was found to be associated with ERα overexpression. Mechanistic investigations suggested that RhoB modulates ERα expression, controlling both its protein and mRNA levels, and that RhoB modulates PR expression by accentuating the recruitment of ERα and other major co-regulators to the promoter of PR gene. A major consequence of RhoB modulation was that RhoB differentially regulated the proliferation of breast cancer cell lines. Interestingly, we documented crosstalk between RhoB and ERα, with estrogen treatment leading to RhoB activation.
  
  
  CONCLUSIONS
  Taken together, our findings offer evidence that in human breast cancer RhoB acts as a positive function to promote expression of ERα and PR in a manner correlated with cell proliferation.
authors: Claire
authors: C
authors: Médale-Giamarchi
authors: Isabelle
authors: I
authors: Lajoie-Mazenc
authors: Emilie
authors: E
authors: Malissein
authors: Elise
authors: E
authors: Meunier
authors: Bettina
authors: B
authors: Couderc
authors: Yann
authors: Y
authors: Bergé
authors: Thomas
authors: T
authors: Filleron
authors: Laura
authors: L
authors: Keller
authors: Claudine
authors: C
authors: Marty
authors: Magali
authors: M
authors: Lacroix-Triki
authors: Florence
authors: F
authors: Dalenc
authors: Sophie F
authors: SF
authors: Doisneau-Sixou
authors: Gilles
authors: G
authors: Favre
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D020743:rhoB GTP-Binding Protein