Guo Y, Sklar G N, Borkowski A, Kyprianou N
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Clin Cancer Res. 1997 Dec;3(12 Pt 1):2269-74.
Loss of expression or mutational deletion of the cyclin-dependent kinase inhibitor p27(Kip1) has recently been implicated in malignant development. In this study, we investigated the relationship between p27(Kip1) protein expression and tumor grade in human prostate cancer by conducting an immunohistochemical analysis in a series of normal prostate, benign prostatic hyperplasia, and malignant prostate cancer specimens. The proliferative activity of prostatic tumors was determined on the basis of the Ki-67 nuclear antigen staining. A uniformly intense immunoreactivity for p27(Kip1) was localized to the nuclei of glandular epithelial cells of normal prostates. The benign glandular epithelia exhibited moderate immunostaining. In the malignant prostate tissue, however, a heterogeneous pattern of substantially reduced p27(Kip1) immunoreactivity was found among the glandular epithelial cells. The majority of primary prostate cancer specimens (68%) were totally negative for p27(Kip1) immunoreactivity, whereas the rest exhibited a significantly decreased p27(Kip1) expression, compared with the normal prostate (P < 0.01). Moreover, there was progressively diminished p27(Kip1) immunostaining with increased tumor grade. This loss of p27(Kip1) was associated with an increase in the proliferative index of prostatic tumors (r = 0.88). There was no significant relationship between p27(Kip) loss and the transforming growth factor beta receptor status of prostatic adenocarcinomas. These results indicate that frequent loss of the cyclin-dependent kinase inhibitor p27(Kip1) in human prostate cancer cells correlates with advancing histological aggressiveness, implicating deregulation of p27(Kip1) in prostate tumor progression.
细胞周期蛋白依赖性激酶抑制剂p27（Kip1）表达缺失或突变性缺失最近被认为与恶性肿瘤发展有关。在本研究中，我们通过对一系列正常前列腺、良性前列腺增生和恶性前列腺癌标本进行免疫组织化学分析，研究了人前列腺癌中p27（Kip1）蛋白表达与肿瘤分级之间的关系。基于Ki-67核抗原染色确定前列腺肿瘤的增殖活性。正常前列腺腺上皮细胞核呈现出均匀强烈的p27（Kip1）免疫反应性。良性腺上皮表现出中度免疫染色。然而，在恶性前列腺组织中，腺上皮细胞中发现了p27（Kip1）免疫反应性显著降低的异质性模式。大多数原发性前列腺癌标本（68%）p27（Kip1）免疫反应性完全阴性，而其余标本与正常前列腺相比，p27（Kip1）表达显著降低（P < 0.01）。此外，随着肿瘤分级增加，p27（Kip1）免疫染色逐渐减弱。p27（Kip1）缺失与前列腺肿瘤增殖指数增加相关（r = 0.88）。p27（Kip）缺失与前列腺腺癌的转化生长因子β受体状态之间无显著关系。这些结果表明，人前列腺癌细胞中细胞周期蛋白依赖性激酶抑制剂p27（Kip1）的频繁缺失与组织学侵袭性增加相关，提示p27（Kip1）失调在前列腺肿瘤进展中起作用。
