CYCLIN D1 PROTEIN EXPRESSION AND FUNCTION IN HUMAN BREAST-CANCER
CYCLIN D1 PROTEIN EXPRESSION AND FUNCTION IN HUMAN BREAST-CANCER
复制标题
DOI：
10.1002/ijc.2910570311
复制
发表时间：
1994-05-01
影响因子：
6.4
通讯作者：
BARTEK, J
中科院分区：
文献类型：
--
作者：
BARTKOVA, J;LUKAS, J;BARTEK, J
细胞周期蛋白D1是G（1）期进展所必需的细胞周期调节因子，也是与包括乳腺癌在内的几种人类肿瘤类型的发病机制有关的候选原癌基因。尽管积累的遗传学证据，但是，没有关于乳腺癌中细胞周期蛋白D1蛋白的丰度和性质的数据。我们现在报告异常核过表达/积累的细胞周期蛋白D1蛋白在约一半的170例原发性乳腺癌标本单克隆抗体免疫组化分析，表明细胞周期蛋白D1异常的频率可能是相当高的比以前推断的DNA扩增研究。对肿瘤进展不同阶段匹配病变中的表达模式进行比较表明，细胞周期蛋白D1蛋白异常似乎反映了相对早期的事件，并且当被肿瘤获得时，它在整个乳腺癌进展（包括转移性扩散）过程中保持不变。在肿瘤组织和乳腺癌细胞系中，这种蛋白质的丰度显示出与细胞周期振荡和G（1）中表达的峰值水平一致的特征性变化。在视网膜母细胞瘤（Rb）蛋白突变或与SV 40 T抗原复合的所有7个细胞系中，抗体介导的和反义寡核苷酸敲除实验表明，细胞周期蛋白D1蛋白和mRNA的水平异常低。在具有单拷贝或多拷贝基因的乳腺癌细胞系中细胞周期蛋白D1的周期调节功能，并揭示细胞中不存在这种要求有RB缺陷的线路。我们的数据与新出现的Rb-细胞周期蛋白D1通路是乳腺癌致癌异常的常见靶点的观点一致。(C)1994 Wiley-Liss，Inc.
Cyclin D1 is a cell-cycle regulator essential for G(1) phase progression and a candidate proto-oncogene implicated in pathogenesis of several human tumour types, including breast carcinomas. In spite of the accumulating genetic evidence, however, there are no data regarding abundance and properties of the cyclin D1 protein in breast cancer. We now report aberrant nuclear overexpression/accumulation of the cyclin D1 protein in about half of the 170 primary breast carcinoma specimens analyzed by monoclonal antibody immunohistochemistry, indicating that the frequency of cyclin D1 abnormalities may be considerably higher than previously deduced from DNA amplification studies. A comparison of the expression patterns in matched lesions at different stages of tumour progression revealed that the cyclin D1 protein aberration appears to reflect a relatively early event and that, when acquired by a tumour, it is maintained throughout breast cancer progression including metastatic spread. In both tumour tissues nd breast cancer cell lines, the abundance of this protein shows characteristic variations consistent with a cell-cycle oscillation and the peak levels expressed in G(1). In all 7 cell lines whose retinoblastoma (Rb) protein is mutant or complexed to SV40 T antigen, exceptionally low levels of cyclin D1 protein and mRNA were found. Antibody-mediated and anti-sense oligonucleotide knockout experiments demonstrate the requirement for the cell-cycle regulatory function of cyclin D1 in breast cancer lines with single or multiple copies of the gene and reveal the absence of such a requirement in the cell lines with RB defects. Our data are consistent with the notion that the emerging ''Rb-cyclin D1 pathway'' represents a frequent target on oncogenic abnormalities in breast cancer. (C) 1994 Wiley-Liss, Inc.