title: [TGF-α increases neuroendocrine differentiation and strengthens chemoresistance in prostate cancer DU145 cells].
abstract: OBJECTIVE
  To study whether TGF-α possesses similar EGF effect of enforcing neuroendocrine differentiation (NED) in prostate cancer cell line DU145 and determine the influence of NED induced by TGF-α on chemoresistance.
  
  
  METHODS
  DU145 cells were divided into 3 groups: a group with 2% FBS, a group with 2%FBS+TGF-α 5 ng/mL and a group with 2%FBS+TGF-α 10 ng/mL. Morphological change in DU145 cells was observed after TGF-α treatment. Expression levels of NSE mRNA were detected with real time RT-PCR. Western blot was used to detect the expression levels of protein NSE, P-gp, MRP1 and Bcl-2. Cell cycles of DU145 cells in the 3 groups were examined with flow cytometry. MTT assay was used to evaluate the influence of TGF-α in chemoresistance.
  
  
  RESULTS
  Compared with DU145 cells cultured with 2% FBS, cells treated with 2% FBS+TGF-α were pleomorphic and pseudopodia extended. The expression level of NSE mRNA upregulated to (3.6±0.5) folds (P<0.05) and (10.1±0.1) folds (P<0.01). Western blot showed that the expression levels of protein NSE, Bcl-2, and MRP1 increased after treatment with different concentrations of TGF-α; P-gp was not detected. The proportion of DU145 cells in phase G1 decreased; proportions of cells in phase S and phase G2/M were increased after TGF-α treatment (5 μg/mL). At the same time, chemoresistance of DU145 cells to cisplatin increased.
  
  
  CONCLUSIONS
  TGF-α can increase NED in DU145 cells and enforce the chemoresistance to cisplatin.
authors: Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
authors: Jun
authors: J
authors: Wang
authors: Xiongbing
authors: X
authors: Zu
authors: Yuan
authors: Y
authors: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D056827:Endosomal Sorting Complexes Required for Transport / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C498543:CHMP3 protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D016211:Transforming Growth Factor alpha; D002945:Cisplatin