title: CTEN/tensin 4 expression induces sensitivity to paclitaxel in prostate cancer.
abstract: BACKGROUND
  Recently, we established paclitaxel-resistant prostate cancer cell lines (PC-3-TxR and DU145-TxR). To determine the mechanisms of paclitaxel resistance in PC-3-TxR cells, we compared the gene expression profiles between PC-3 and PC-3-TxR cells. Our results indicated that expression of the C-terminal tensin like protein (CTEN, tensin 4) gene was down-regulated by 10-fold in PC-3-TxR cells. We investigated the possibility that CTEN overexpression restores paclitaxel sensitivity.
  
  
  METHODS
  We investigated how knockdown and overexpression of CTEN in androgen-independent cell lines affect paclitaxel sensitivity by colony formation assay and growth inhibition assay. To determine the mechanisms by which CTEN affects paclitaxel sensitivity, we investigated the relationships between CTEN and F-actin or epidermal growth factor receptor (EGFR) in PC-3 cells. We also examined the association between expression of CTEN and grade of prostate cancer by immunohistochemistry using tissue microarray analysis.
  
  
  RESULTS
  Down-regulation of CTEN, which is located in the cytoskeleton, played an important role in paclitaxel resistance in PC-3-TxR cells. Knockdown of CTEN expression in PC-3 cells induced paclitaxel resistance. Overexpression of CTEN in PC-3-TxR and DU145-TxR cells restored paclitaxel sensitivity. CTEN expression was inversely correlated with F-actin and EGFR expression. Then knockdown of actin and EGFR in PC-3-TxR cells recovered paclitaxel sensitivity, indicating that CTEN down-regulation mediates paclitaxel resistance through elevation of EGFR and actin expression. Moreover, CTEN expression was inversely correlated with Gleason score.
  
  
  CONCLUSIONS
  These results strongly suggested that CTEN plays an important role in paclitaxel sensitivity and that CTEN expression level may be a prognostic predictive factor for PCa patients.
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: YouQiang
authors.initials: Y
authors.lastname: Li
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizokami
authors.forename: Kouji
authors.initials: K
authors.lastname: Izumi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Narimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Shima
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinlu
authors.initials: J
authors.lastname: Dai
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000070876:Tensins
chemical_list: D008840:Microfilament Proteins; C000603371:TNS4 protein, human; D000070876:Tensins; D017239:Paclitaxel