title: Establishment and characterization of androgen-independent human prostate cancer LNCaP cell model.
abstract: BACKGROUND
  The acquisition of an androgen-independent phenotype is the most serious issue of prostate cancer treatment. Although several experimental cell models have been reported for studying androgen independence, they have limited applications related to hormone-refractory prostate cancer. To investigate the molecular mechanism of androgen-independent growth of prostate cancer, we established a useful LNCaP cell model that resembles the clinical scenario of hormone-refractory prostate cancer.
  
  
  METHODS
  Androgen-sensitive LNCaP parental cells were continuously maintained in a regular cell-culture medium, that is, phenol red-positive RPMI 1640 medium supplemented with 5% fetal bovine serum and 1% glutamine. Upon passage, the androgen responsiveness of those cells decreased, to a level lower than that of parental cells. We examined the growth properties and androgen responsiveness of these different LNCaP cells in vitro and in vivo. Cytogenetic characteristics and expression of androgen receptors (ARs) and prostate-specific antigen (PSA) were determined.
  
  
  RESULTS
  Upon continuous passage, the biological behavior of parental C-33 cells (passage number less than 33) was altered. C-81 cells (passage number higher than 81) clearly exhibited more aggressive growth and lower androgen responsiveness than C-33 and C-51 cells (passage number between 35 and 80) in vitro and in vivo. Nevertheless, all these cells expressed a similar level of functional AR protein as well as a similar genetic profile. Moreover, in a steroid-reduced culture condition, C-81 cells secreted a higher level of PSA than C-33 cells.
  
  
  CONCLUSIONS
  Our LNCaP cell model closely recapitulates the progression of human prostate cancer from the androgen-responsive to the hormone-refractory state under the androgen nondeprived condition. This cell model may provide the opportunity to understand the molecular mechanisms associated with the acquisition of androgen independence during human prostate cancer progression.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-4525, USA.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Igawa
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Lin
authors.forename: Ming-Shyue
authors.initials: MS
authors.lastname: Lee
authors.forename: Dev
authors.initials: D
authors.lastname: Karan
authors.forename: Surinder K
authors.initials: SK
authors.lastname: Batra
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Lin
mesh_terms: D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D020732:Cytogenetic Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D004273:DNA, Neoplasm; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen