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

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 c...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 1999-10, Vol.91 (20), p.1758-1764
Main Authors: BUBENDORF, L, KOLMER, M, ELKAHLOUN, A. G, PRETLOW, T. G, GASSER, T. C, MIHATSCH, M. J, SAUTER, G, KALLIONIEMI, O.-P, KONONEN, J, KOIVISTO, P, MOUSSES, S, CHEN, Y, MAHLAMÄKI, E, SCHRAML, P, MOCH, H, WILLI, N
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Hormonal - therapeutic use
Biological and medical sciences
Deoxyribonucleic acid
DNA
DNA, Complementary - analysis
DNA, Complementary - drug effects
DNA, Neoplasm - analysis
DNA, Neoplasm - drug effects
Gene Expression Regulation, Neoplastic - drug effects
Genes
Genetics
Heat-Shock Proteins - analysis
Heat-Shock Proteins - genetics
Humans
Immunohistochemistry
Insulin-Like Growth Factor Binding Protein 2 - analysis
Insulin-Like Growth Factor Binding Protein 2 - genetics
Male
Medical diagnosis
Medical sciences
Mice
Mice, Nude
Neoplasm Recurrence, Local
Nephrology. Urinary tract diseases
Prostate cancer
Prostatic Hyperplasia - genetics
Prostatic Neoplasms - chemistry
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - genetics
Reverse Transcriptase Polymerase Chain Reaction
Scientific imaging
Tissues
Transplantation, Heterologous
Treatment Failure
Tumors of the urinary system
Urinary tract. Prostate gland
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Summary: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. 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. 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). 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.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/91.20.1758