Hormone Therapy Failure in Human Prostate Cancer: Analysis by Complementary DNA and Tissue Microarrays
📄 阅读原文（OpenAlex）↗📝 摘要
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.
🧾 论文要素
| 作者 | Lukas Bubendorf; Meelis Kolmer; Juha Kononen; Pasi A. Koivisto; Spyro Mousses; Y. Chen; Eija Mahlamäki; Peter Schraml; Holger Moch; Niels Willi; ABDEL G. ELKAHLOUN; T G Pretlow; Thomas Christian Gasser; Michael Jörg Mihatsch; Guido Sauter; Olli Kallioniemi |
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| 期刊 | JNCI Journal of the National Cancer Institute |
| 出版机构 | https://openalex.org/P4310311648 |
| 年份 | 1999 |
| 归属类 | 前列腺癌 |
| 平台 | OpenAlex |
| 被引数 | 350 |
| 阅读量 | 8 |
| DOI | 10.1093/jnci/91.20.1758 ↗ |
| 关键词 | Prostate cancer; Tissue microarray; Prostate; Microarray; Cancer |