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Titre du document / Document title

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

Auteur(s) / Author(s)

BUBENDORF L. (1) ; KOLMER M. (1) ; KONONEN J. (1) ; KOIVISTO P. (2) ; MOUSSES S. (1) ; CHEN Y. (1) ; MAHLAMÄKI E. (2) ; SCHRAML P. (3) ; MOCH H. (3) ; WILLI N. (3) ; ELKAHLOUN A. G. (4) ; PRETLOW T. G. (5) ; GASSER T. C. (6) ; MIHATSCH M. J. (3) ; SAUTER G. (3) ; KALLIONIEMI O.-P. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, MD, ETATS-UNIS
(2) Laboratory of Cancer Genetics, Tampere University Hospital, FINLANDE
(3) Institute of Pathology, University of Basel, SUISSE
(4) Research Genetics, Inc., Huntsville, AL, ETATS-UNIS
(5) Institute of Pathology, Case Western Reserve University, Cleveland, OH, ETATS-UNIS
(6) Urologic Clinics, University of Basel, SUISSE

Résumé / 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 over-expressed 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.

Revue / Journal Title

Journal of the National Cancer Institute    ISSN  0027-8874 

Source / Source

1999, vol. 91, no20, pp. 1758-1764 (46 ref.)

Langue / Language

Anglais

Editeur / Publisher

Oxford University Press, Cary, NC, ETATS-UNIS  (1940) (Revue)

Mots-clés anglais / English Keywords

Adenocarcinoma

;

Prostate

;

Androgen

;

Negative therapeutic reaction

;

Immunohistochemistry

;

Comparative genomic hybridization

;

Cytogenetics

;

Polymerase chain reaction

;

Gene expression

;

Implantation

;

Comparative study

;

Tumor progression

;

Human

;

Male

;

Established cell line

;

Animal

;

Mouse

;

Rodentia

;

Mammalia

;

Vertebrata

;

Malignant tumor

;

Urinary system disease

;

Male genital diseases

;

Prostate disease

;

Sex steroid hormone

;

Pathology

;

Molecular biology

;

Mots-clés français / French Keywords

Adénocarcinome

;

Prostate

;

Androgène

;

Résistance traitement

;

Immunohistochimie

;

Hybridation génomique comparative

;

Cytogénétique

;

Réaction chaîne polymérase

;

Expression génique

;

Implantation

;

Etude comparative

;

Progression carcinogenèse

;

Homme

;

Mâle

;

Lignée cellulaire établie

;

Animal

;

Souris

;

Méthode microarray

;

Mutation NUDE (nu)

;

Rodentia

;

Mammalia

;

Vertebrata

;

Tumeur maligne

;

Appareil urinaire pathologie

;

Appareil génital mâle pathologie

;

Prostate pathologie

;

Hormone stéroïde sexuelle

;

Anatomopathologie

;

Biologie moléculaire

;

Mots-clés espagnols / Spanish Keywords

Adenocarcinoma

;

Prostata

;

Andrógeno

;

Resistencia al tratamiento terapeútico

;

Inmunohistoquímica

;

Hibridación genómica comparativa

;

Citogenética

;

Reacción cadena polimerasa

;

Expresión genética

;

Implantación

;

Estudio comparativo

;

Progresión carcinogénesis

;

Hombre

;

Macho

;

Línea celular establecida

;

Animal

;

Ratón

;

Rodentia

;

Mammalia

;

Vertebrata

;

Tumor maligno

;

Aparato urinario patología

;

Aparato genital macho patología

;

Prostata patología

;

Hormona esteroide sexual

;

Anatomía patológica

;

Biología molecular

;

Localisation / Location

INIST-CNRS, Cote INIST : 3364, 35400008114473.0080

Nº notice refdoc (ud4) : 1241283



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