title: RhoC and guanine nucleotide exchange factor Net1 in androgen-unresponsive mouse mammary carcinoma SC-4 cells and human prostate cancer after short-term endocrine therapy.
abstract: BACKGROUND
  Endocrine resistance is a critical issue in managing patients with prostate cancer. This study is undertaken to search for a potential molecular target connected with this process using a model system of androgen-dependent and androgen-unresponsive SC-3 and SC-4 cells.
  
  
  METHODS
  Expression profiles, actin stress fiber organization, and the levels of activated Rho GTPases were compared between SC-4 and SC-3 cells using an oligonucleotide microarray, phalloidin staining, and a Rho activation assay. The cell viability was analyzed with a Rho inhibitor or by stable transfection with either a dominant-negative (DN) form of RhoC or a mutant form of NET1 (mutNET1). The expressions of RhoC, NET1, and epithelial-mesenchymal transition (EMT) markers were immunohistochemically analyzed in human prostate cancer specimens after short-term endocrine therapy and in an untreated condition.
  
  
  RESULTS
  SC-4 cells exhibited mesenchymal phenotypes with activation of Rho signals. Treatment with a Rho inhibitor suppressed the cell viability in SC-4 cells, but not in SC-3 cells. The cell viability of SC-4 cells stably expressing DN-RhoC and mutNET1 was also attenuated. In the immunohistochemical analysis, NET1 and the EMT marker of N-cadherin were expressed at higher levels in prostate cancers after short-term endocrine therapy than in untreated tumors, and RhoC expression was maintained after short-term endocrine therapy.
  
  
  CONCLUSIONS
  Rho signaling is involved in the cell survival of SC-4 cells. The higher expressions of RhoC and NET1 in human prostate cancers after short-term endocrine therapy suggest that RhoC and NET1 may become therapeutic targets during endocrine therapy.
authors.affiliation: Department of Pathology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kawata
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kamiakito
authors.forename: Kenji
authors.initials: K
authors.lastname: Komatsu
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Morita
authors.forename: Toshio
authors.initials: T
authors.lastname: Ota
authors.forename: Masaya
authors.initials: M
authors.lastname: Obayashi
authors.forename: Kenya
authors.initials: K
authors.lastname: Shitara
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage*; D000728:Androgens / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D015513:Oncogene Proteins / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000075024:rhoC GTP-Binding Protein
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D020662:Guanine Nucleotide Exchange Factors; C099763:NET1 protein, human; D015513:Oncogene Proteins; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein