Comstock C E S, Revelo M P, Buncher C R, Knudsen K E
Department of Cell and Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Br J Cancer. 2007 Mar 26;96(6):970-9. doi: 10.1038/sj.bjc.6603615.
Cyclin D1 is a critical regulator of androgen-dependent transcription and cell cycle progression in prostate cancer cells. Despite the influence of D-type cyclins on prostate cancer proliferation, few studies have examined the expression of cyclin D1 in localised tumours or challenged its relevance to disease progression. Cyclin D1 status was characterised using immunohistochemistry in 38 non-neoplastic prostate samples, 138 primary human prostate carcinomas, and three lymph node metastatic specimens. Relevance of cyclin D1 to preoperative prostate-specific antigen (PSA) levels, Ki-67 index, and p21Cip1 status was also examined. Cyclin D1-positive phenotype was increased in primary carcinoma compared to non-neoplastic tissue, and was evident in all lymph node metastases cases. Interestingly, at least three distinct localisation patterns were observed in the cyclin D1-positive cohort, wherein cytoplasmic localisation was identified in a large fraction, and this pattern was predominant in lower grade tumours. Relevance of altered cyclin D1 status was observed, wherein cyclin D1-positive tumours were associated with low preoperative PSA levels, consistent with in vitro reports that cyclin D1 may alter the expression of this tumour marker. Moreover, tumours with predominantly cytoplasmic cyclin D1 showed the lowest Ki-67 index, whereas nuclear cyclin D1 was associated with higher grade, elevated Ki-67, and increased nuclear p21Cip1. These data demonstrate that differential cyclin D1 status may influence clinicopathological parameters, and reveal new insight as to the regulation and potential consequence of cyclin D1 expression in prostate cancer.
细胞周期蛋白D1是前列腺癌细胞中雄激素依赖性转录和细胞周期进程的关键调节因子。尽管D型细胞周期蛋白对前列腺癌增殖有影响,但很少有研究检测细胞周期蛋白D1在局限性肿瘤中的表达,或质疑其与疾病进展的相关性。使用免疫组织化学对38个非肿瘤性前列腺样本、138例原发性人类前列腺癌和3个淋巴结转移标本进行细胞周期蛋白D1状态的特征分析。还检测了细胞周期蛋白D1与术前前列腺特异性抗原(PSA)水平、Ki-67指数和p21Cip1状态的相关性。与非肿瘤组织相比,原发性癌中细胞周期蛋白D1阳性表型增加,并且在所有淋巴结转移病例中均很明显。有趣的是,在细胞周期蛋白D1阳性队列中观察到至少三种不同的定位模式,其中大部分为细胞质定位,并且这种模式在低级别肿瘤中占主导。观察到细胞周期蛋白D1状态改变的相关性,其中细胞周期蛋白D1阳性肿瘤与术前低PSA水平相关,这与体外报告一致,即细胞周期蛋白D1可能改变这种肿瘤标志物的表达。此外,主要为细胞质细胞周期蛋白D1的肿瘤显示出最低的Ki-67指数,而细胞核细胞周期蛋白D1与更高级别、升高的Ki-67和增加的细胞核p21Cip1相关。这些数据表明,细胞周期蛋白D1状态的差异可能影响临床病理参数,并揭示了关于前列腺癌中细胞周期蛋白D1表达的调节及其潜在后果的新见解。