title: Down-regulation of CD9 expression during prostate carcinoma progression is associated with CD9 mRNA modifications.
abstract: OBJECTIVE
  Cluster-of-differentiation antigen 9 (CD9) protein, a member of the tetraspanin family, has been implicated in carcinogenesis of various human tumors. Although decreased expression of the CD82 tetraspanin protein, a close CD9 relative, is associated with prostate cancer progression, CD9 expression has not been analyzed in this malignancy.
  
  
  METHODS
  CD9 expression in human prostatic adenocarcinoma was analyzed by immunohistochemistry on 167 primary tumors and 88 lymph node or bone metastases. CD9 cDNA was sequenced from two human prostate cancer cell lines, prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and normal prostatic tissues.
  
  
  RESULTS
  Although CD9 was detected in the epithelium of normal prostatic tissues, reduced or loss of CD9 expression within neoplastic cells was observed in 24% of 107 clinically localized primary adenocarcinomas, 85% of 60 clinically advanced primary adenocarcinomas, 85% of 65 lymph node metastases, and 65% of 23 bone metastases. Difference in CD9 expression between clinically localized and advanced diseases was highly significant (P < 1 x 10(-7)). Whereas there was no alteration of CD9 cDNA in normal tissues, all PC-3-derived cell lines, one PIN, and four prostatic adenocarcinomas harbored deletions in their CD9 cDNAs. Recurring CD9 point mutations were also found in PC-3M-LN4 cells, one PIN, and seven prostatic adenocarcinomas.
  
  
  CONCLUSIONS
  CD9 expression is significantly reduced and even lost during prostate cancer progression. Moreover, deletions and mutations of the CD9 mRNA may be associated with loss of protein expression observed in tumor cells. Our data suggest that CD9 inactivation may play an important role in prostate cancer progression.
authors.affiliation: McMaster University Medical Centre, Hamilton, Ontario, Canada.
authors.forename: Jia-Chi
authors.initials: JC
authors.lastname: Wang
authors.forename: Louis R
authors.initials: LR
authors.lastname: Bégin
authors.forename: Nathalie G
authors.initials: NG
authors.lastname: Bérubé
authors.forename: Simone
authors.initials: S
authors.lastname: Chevalier
authors.forename: Armen G
authors.initials: AG
authors.lastname: Aprikian
authors.forename: Henriette
authors.initials: H
authors.lastname: Gourdeau
authors.forename: Mario
authors.initials: M
authors.lastname: Chevrette
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015703:Antigens, CD / Q000235:genetics*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics; D060245:Tetraspanin 29
chemical_list: D015703:Antigens, CD; C554869:CD9 protein, human; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D060245:Tetraspanin 29