Fulltext

Hormone Therapy Failure in Human Prostate Cancer: Analysis by Complementary DNA andTissue Microarrays

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

In: Journal of the National Cancer Institute, 1999, vol. 91, no. 20, p. 1758-1764

Zum persönliche Liste hinzufügen
    Titel
    • Hormone Therapy Failure in Human Prostate Cancer: Analysis by Complementary DNA andTissue Microarrays
    Autor
    • Bubendorf, Lukas
    • Kolmer, Meelis
    • Kononen, Juha
    • Koivisto, Pasi
    • Mousses, Spyro
    • Chen, Yidong
    • Mahlamäki, Eija
    • Schraml, Peter
    • Moch, Holger
    • Willi, Niels
    • Elkahloun, Abdel G.
    • Pretlow, Thomas G.
    • Gasser, Thomas C.
    • Mihatsch, Michael J.
    • Sauter, Guido
    • Kallioniemi, Olli-P. Affiliations of authors:L. Bubendorf, M. Kolmer, J. Kononen, S. Mousses, Y. Chen, O.-P. Kallioniemi, Cancer GeneticsBranch, National Human Genome Research Institute, Bethesda, MD; P.Koivisto, E. Mahlamäki, Laboratory of Cancer Genetics, TampereUniversity Hospital, Finland; P. Schraml, H. Moch, N. Willi, M. J.Mihatsch, G. Sauter (Institute of Pathology), T. C. Gasser (UrologicClinics), University of Basel, Switzerland; A. G. Elkahloun, ResearchGenetics, Inc., Huntsville, AL; T. G. Pretlow, Institute of Pathology,Case Western Reserve University, Cleveland, OH.
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Journal of the National Cancer Institute, 1999, vol. 91, no. 20, p. 1758-1764. Oxford University Press
    Andere elektronische Ausgabe
    Klassifikation
    • Gesundheit
    OAI-PMH-ID
    • oai:doc.rero.ch:297307
    Summary
    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