title: Molecular alterations associated with LNCaP cell progression to androgen independence.
abstract: BACKGROUND
  There is no effective therapy currently available for androgen-independent (AI) prostate cancer (CaP). This is largely due to lack of information about the molecular mechanisms by which androgen-dependent tumor cells progress to androgen independence. In this study, we investigated molecular alterations occurring in AI LNCaP cells.
  
  
  METHODS
  We established and characterized three AI LNCaP sublines that exhibited a wide range of cytogenetic alterations. In order to understand why androgen-sensitive LNCaP cells can survive in an androgen-deprived environment, we analyzed the expression of signaling proteins associated with proliferation and survival of AI cells. In addition, gene expression profiling was performed to gain insight into molecular alterations in these LNCaP sublines.
  
  
  RESULTS
  These LNCaP sublines exhibited heightened levels of androgen receptor (AR), HER2, MAPK, serine 473-phosphorylated Akt, and Bcl-2, implicating these proteins as mediators of AI growth. Gene expression profiling identified a common set of 66 genes that were differentially expressed in all three sublines compared to the parental LNCaP cells. Of these, 32 were apparently androgen regulated, while the remainder comprised an expression signature specific for androgen independence.
  
  
  CONCLUSIONS
  We have developed AI LNCaP cell models and identified several genes that are specifically expressed in these models. Elucidating the relative importance of these genetic changes will help define the molecular mechanism by which CaP progresses to androgen independence.
authors.affiliation: Department of Urology, University of California, Davis, School of Medicine, Sacramento, California 95817, USA.
authors.forename: Xu-Bao
authors.initials: XB
authors.lastname: Shi
authors.forename: Ai-Hong
authors.initials: AH
authors.lastname: Ma
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Tepper
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Gregg
authors.forename: Regina
authors.initials: R
authors.lastname: Gandour-Edwards
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: Hsing-Jien
authors.initials: HJ
authors.lastname: Kung
authors.forename: Ralph W
authors.initials: RW
authors.lastname: deVere White
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D015152:Blotting, Northern; D002455:Cell Division; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D019254:Genes, bcl-2 / Q000235:genetics; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D011944:Receptors, Androgen / Q000032:analysis* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D020929:Mitogen-Activated Protein Kinase Kinases