Hormone therapy failure in human prostate cancer: Analysis by complementary DNA and tissue microarrays

Lukas Bubendorf, Meelis Kolmer, Juha Kononen, Pasi Koivisto, Spyro Mousses, Yidong Chen, Eija Mahlamäki, Peter Schraml, Holger Moch, Niels Willi, Abdel G. Elkahloun, Thomas G. Pretlow, Thomas C. Gasser, Michael J. Mihatsch, Guido Sauter, Olli P. Kallioniemi

Research output: Contribution to journalArticlepeer-review

317 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1758-1764
Number of pages7
JournalJournal of the National Cancer Institute
Volume91
Issue number20
DOIs
StatePublished - Oct 20 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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