title: Hormone therapy failure in human prostate cancer: analysis by complementary DNA and tissue microarrays.
abstract: BACKGROUND
  The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies.
  
  
  METHODS
  Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used for immunohistochemical detection of protein expression.
  
  
  RESULTS
  Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001).
  
  
  CONCLUSIONS
  The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory state and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer.
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bubendorf
authors.forename: M
authors.initials: M
authors.lastname: Kolmer
authors.forename: J
authors.initials: J
authors.lastname: Kononen
authors.forename: P
authors.initials: P
authors.lastname: Koivisto
authors.forename: S
authors.initials: S
authors.lastname: Mousses
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: E
authors.initials: E
authors.lastname: Mahlamäki
authors.forename: P
authors.initials: P
authors.lastname: Schraml
authors.forename: H
authors.initials: H
authors.lastname: Moch
authors.forename: N
authors.initials: N
authors.lastname: Willi
authors.forename: A G
authors.initials: AG
authors.lastname: Elkahloun
authors.forename: T G
authors.initials: TG
authors.lastname: Pretlow
authors.forename: T C
authors.initials: TC
authors.lastname: Gasser
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: G
authors.initials: G
authors.lastname: Sauter
authors.forename: O P
authors.initials: OP
authors.lastname: Kallioniemi
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018076:DNA, Complementary / Q000032:analysis / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D017211:Treatment Failure
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D006360:Heat-Shock Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2