Koumakpayi Ismaël Hervé, Diallo Jean-Simon, Le Page Cécile, Lessard Laurent, Gleave Martin, Bégin Louis R, Mes-Masson Anne-Marie, Saad Fred
Centre de recherche du Centre hospitalier de l'Université de Montréal and Institut du cancer de Montréal, Quebec, Canada.
Clin Cancer Res. 2006 May 1;12(9):2730-7. doi: 10.1158/1078-0432.CCR-05-2242.
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.
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.
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).
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.
表皮生长因子受体1（ErbB1）和表皮生长因子受体2（ErbB2）已被证实与前列腺癌进展相关，但对于其他表皮生长因子受体（ErbB）家族成员在前列腺癌中的作用及生物学特性了解较少。本研究旨在分析ErbB3在前列腺组织和前列腺癌细胞系中的表达及定位情况。
对143例患者的前列腺癌组织切片以及包含81例患者根治性前列腺切除术标本的390个核心组织微阵列进行ErbB3免疫组织化学检测，这些标本代表正常组织、前列腺上皮内瘤变组织及恶性组织。通过蛋白质印迹分析研究ErbB3在LNCaP、22Rv1、PC-3和DU145前列腺癌细胞系中的亚细胞定位。
前列腺癌组织的免疫组织化学分析显示，超过90%的前列腺癌组织呈现细胞质ErbB3染色。在正常前列腺组织和良性前列腺增生组织中观察到极少的ErbB3细胞核染色；相反，ErbB3常定位于癌组织细胞核中。与激素敏感样本（92例中的37例，40.2%）相比，这种细胞核定位在激素难治性组织中更常见（17例中的17例，100%，P<0.001）。此外，在组织微阵列中，细胞核内ErbB3增加与Gleason分级增加相关。有趣的是，细胞质和细胞核亚细胞组分的蛋白质印迹分析表明，与激素不敏感细胞系（PC-3和DU145）相比，ErbB3细胞核定位在激素敏感前列腺癌细胞系（LNCaP和22Rv1）中更普遍。
ErbB3细胞核定位可区分正常与恶性前列腺组织，以及激素敏感型与激素难治型前列腺癌肿瘤。ErbB3细胞核染色似乎与疾病进展风险相关。ErbB3在激素难治性组织中的高频率细胞核定位表明，ErbB3值得进一步研究以了解其与前列腺癌疾病进展的关联。
