title: [Changes of intracellular cholesterol metabolism in neuroendocrine differentiation of prostate cancer and their significance].
abstract: OBJECTIVE
  To explore the roles of intracellular cholesterol metabolism in neuroendocrine (NE) differentiation of prostate cancer based on an androgen-independent prostate cancer NE cell model induced by androgen deprivation.
  
  
  METHODS
  LNCaP cells were cultured in androgen-depleted medium, and NE phenotypes were identified by observing the changes in cell morphology, molecular markers (SgIII, NSE and CgA) and cell proliferation. The expression and distribution of cholesterol and Sg III were determined by immunofluorescence staining. The expressions of the key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake were detected by semi-quantitative RT-PCR.
  
  
  RESULTS
  The LNCaP cells showed shrinking bodies and extending axons after androgen deprivation, and all the molecular markers, such as Sg III, NSE and CgA, significantly increased in a time-dependent manner, while the cell proliferation was obviously inhibited (P < 0.05). The cholesterol distribution in the LNCaP cells after NE differentiation presented remarkable aggregation at the axon terminals. However, there were no significant differences in the expression of cholesterol between the two types of cells, nor in the changes of the expressions of key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake (P > 0.05).
  
  
  CONCLUSIONS
  Transient androgen depletion could successfully induce NE differentiation of LNCaP cells, and the intracellular cholesterol could re-distribute into axon terminals to enhance the formation of neurosecretory granules.
authors.affiliation: Department of Medical Imaging, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. rongwang@mail.xjtu.edu.cn
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Xin-Yang
authors.initials: XY
authors.lastname: Wang
authors.forename: Da-Lin
authors.initials: DL
authors.lastname: He
mesh_terms: D000728:Androgens / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008297:Male; D009490:Neurosecretory Systems / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011973:Receptors, LDL / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism
chemical_list: D000728:Androgens; C573412:LDLR protein, human; D011973:Receptors, LDL; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol