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Hormone Therapy Failure in Human Prostate Cancer: Analysis by Complementary DNA and Tissue Microarrays
Open accessAbstract
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.
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Cited by
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Camp, R. L., Charette, L. A., & Rimm, D. L. (2000) · Laboratory Investigation · doi:10.1038/labinvest.3780204 · Cited by 799
Drǎghici, S., Khatri, P., Martins, R. P., Ostermeier, G. C., & Krawetz, S. A. (2003) · Genomics · doi:10.1016/s0888-7543(02)00021-6 · Cited by 578
Holzbeierlein, J., Lal, P., LaTulippe, E., Smith, A., Satagopan, J., Zhang, L., Ryan, C., Smith, S., Scher, H., Scardino, P., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63112-4 · Cited by 577
Androgen Receptor Signaling in Androgen-Refractory Prostate Cancer
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Metadata
- Authors
- Bubendorf, L., Kolmer, M., Kononen, J., Koivisto, P., Mousses, S., Chen, Y., Mahlamaki, E., Schraml, P., Moch, H., Willi, N., Elkahloun, A. G., Pretlow, T. G., Gasser, T. C., Mihatsch, M. J., Sauter, G., & Kallioniemi, O.-P.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-10-20
- Volume
- 91
- Issue
- 20
- Pages
- 1758-1764
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2170677834
- Cited by
- 350
- References
- 0
- FWCI
- 29.66
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Bubendorf, L., Kolmer, M., Kononen, J., Koivisto, P., Mousses, S., Chen, Y., Mahlamaki, E., Schraml, P., Moch, H., Willi, N., Elkahloun, A. G., Pretlow, T. G., Gasser, T. C., Mihatsch, M. J., Sauter, G., & Kallioniemi, O.-P. (1999). Hormone Therapy Failure in Human Prostate Cancer: Analysis by Complementary DNA and Tissue Microarrays. JNCI Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/91.20.1758
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