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Expression and Nuclear Localization of ErbB3 in Prostate Cancer

Authors' Affiliations: ¹ Centre de recherche du Centre hospitalier de l'Université de Montréal and Institut du cancer de Montréal; ² Service d'anatomopathologie, Hôpital du Sacré-Coeur de Montréal; ³ Département de médecine and ⁴ Département d'urologie, Université de Montréal, Montreal, Quebec, Canada; and ⁵ Division of Urology, University of British Columbia, Vancouver, British Columbia, Canada

Requests for reprints: Fred Saad, Centre de recherche du Centre hospitalier de l'Université de Montréal/Hôpital Notre-Dame/Institut du Cancer de Montréal, 1560 rue Sherbrooke est, Montreal, Quebec, Canada H2L 4M1. Phone: 514-890-8000, ext. 27466; Fax: 514-412-7620; E-mail: fred.saad.chum{at}ssss.gouv.qc.ca.

Purpose: The ErbB1 and ErbB2 receptors have been implicated in prostate cancer progression, but less is known about the role and biology of other ErbB receptor family members in prostate cancer. The aim of this study was to analyze the expression and localization of ErbB3 in prostate tissues and prostate cancer cell lines.

Experimental Design: Immunohistochemistry of ErbB3 was done on prostate cancer tissue sections from 143 patients and on a tissue microarray containing 390 cores of radical prostatectomy-derived specimens representing normal, prostatic intraepithelial neoplasia, and malignant tissues from 81 patients. ErbB3 subcellular localization was studied by Western blot analysis in LNCaP, 22Rv1, PC-3, and DU145 prostate cancer cell lines.

Results: Immunohistochemistry analysis of prostate cancer tissues revealed that >90% of prostate cancer tissues displayed cytoplasmic ErbB3 staining. Minimal ErbB3 nuclear staining was observed in normal prostate tissues and benign prostatic hyperplasia tissues; in contrast, ErbB3 was frequently localized in the nucleus of cancerous tissues. This nuclear localization was more frequent (P < 0.001) in hormone-refractory tissues (17 of 17, 100%) compared with hormone-sensitive samples (37 of 92, 40.2%). Additionally, in the tissue microarray, increased nuclear ErbB3 was associated with increasing Gleason grade. Interestingly, Western blot analysis of cytoplasmic and nuclear subcellular fractions showed that ErbB3 nuclear localization was more prevalent in hormone-sensitive prostate cancer cell lines (LNCaP and 22Rv1) compared with hormone-insensitive cell lines (PC-3 and DU145).

Conclusions: ErbB3 nuclear localization discriminates normal from malignant prostate tissues and between tumors from hormone-sensitive versus hormone-refractory prostate cancer. ErbB3 nuclear staining seems to be associated with risk of disease progression. The high frequency of ErbB3 nuclear localization in hormone-refractory tissues indicates that ErbB3 warrants further study to understand its association with prostate cancer disease progression.

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