title: TM4SF1, a novel primary androgen receptor target gene over-expressed in human prostate cancer and involved in cell migration.
abstract: BACKGROUND
  The Androgen Receptor (AR) plays a key role in controlling prostate gland homeostasis and contributes to prostate carcinogenesis. The identification of its target genes should provide new candidates that may be implicated in cancer initiation and progression.
  
  
  METHODS
  Transcriptomic experiments and chromatin immunoprecipitation were combined to identify direct androgen regulated genes. Real-time quantitative PCR (RT-qPCR) analyses were performed to measure TM4SF1 mRNA levels in prostate cancer and benign prostatic hyperplasia (BPH) specimens. Immunohistochemical methods were used to compare TM4SF1 protein expression profiles in the same cohort. A targeted siRNAs knockdown strategy was used, prior to wound healing assays, to analyze the role of TM4SF1 in cell migration in vitro.
  
  
  RESULTS
  We demonstrate for the first time that TM4SF1 is a direct target gene of the AR, a transcription factor of the steroid nuclear receptor family. A functional androgen response element was identified in the promoter region of the gene. In addition, TM4SF1 mRNA expression was higher in cancer samples compared to BPH tissues. The TM4SF1 protein mediates cell motility of prostate cancer cells where it is predominantly localized in the cytoplasm, in contrast to its apical membrane localization in normal prostate epithelial cells.
  
  
  CONCLUSIONS
  Our results reveal a novel function for TM4SF1 in AR signaling. The TM4SF1 mRNA expression is higher in prostate cancer tissues as compared to BPH samples. Inhibition of cell migration after targeted knockdown of TM4SF1 protein expression suggests its contribution to prostate cancer cell metastasis.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Lyon, France. Nathalie.Allioli@recherche.univ-lyon1.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Allioli
authors.forename: Séverine
authors.initials: S
authors.lastname: Vincent
authors.forename: Virginie
authors.initials: V
authors.lastname: Vlaeminck-Guillem
authors.forename: Myriam
authors.initials: M
authors.lastname: Decaussin-Petrucci
authors.forename: Florence
authors.initials: F
authors.lastname: Ragage
authors.forename: Alain
authors.initials: A
authors.lastname: Ruffion
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
chemical_list: C410798:AR protein, human; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; C074075:TM4SF1 protein, human