Cyclin D1 in breast cancer
Cyclin D1 in breast cancer
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DOI：
10.1023/a:1006103831990
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发表时间：
1998-01-01
影响因子：
3.8
通讯作者：
Gillett, CE
中科院分区：
文献类型：
--
作者：
Barnes, DM;Gillett, CE
Cyclin D1蛋白在细胞周期G（1）期调控细胞进程中起重要作用。细胞周期蛋白D1基因CCND 1在大约20%的乳腺癌中扩增，并且该蛋白在大约50%的病例中过表达。这导致了深入的研究，以确定细胞周期蛋白D1是否是乳腺癌的生物标志物;然而，临床工作产生了意想不到的结果。在细胞系和转基因小鼠中的研究表明，CCND 1是一种弱致癌基因，并且预期与c-erbB-2一样，细胞周期蛋白D1蛋白的过度表达将与不良预后相关。早期的免疫组化预后研究产生了模棱两可的结果，但我们，和其他人，最近表明，强染色的细胞周期蛋白D1是更有可能在分化良好，雌激素受体阳性癌。此外，我们发现，细胞周期蛋白D1的过度表达实际上与良好的预后有关，无论是在预后方面还是对内分泌治疗的反应方面。细胞周期蛋白D1经常过度表达在导管原位癌，但不是在良性乳腺疾病，包括不典型导管增生，因此它的表达似乎与癌变密切相关。为了帮助解释细胞周期蛋白D1过表达的明显有益作用，还评估了许多密切相关的细胞周期蛋白，包括细胞周期蛋白依赖性激酶抑制剂p27，其阻断细胞周期蛋白D1的激活作用。最初的报道表明，高水平的p27与良好的预后相关，我们已经证明了p27和细胞周期蛋白D1表达之间的正相关性。细胞周期蛋白D1的这些临床结果是一个例子，说明从基础细胞生物学研究中获得的信息需要通过临床研究来补充，以确定预后标志物的真正价值。
Cyclin D1 protein plays an important part in regulating the progress of the cell during the G(1) phase of the cell cycle. The cyclin D1 gene, CCND1, is amplified in approximately 20% of mammary carcinomas, and the protein is over-expressed in approximately 50% of cases. This has led to intensive study to ascertain whether cyclin D1 is a biological marker in breast cancer; however, the clinical work has produced unexpected results. Work in cell lines and in transgenic mice indicate that CCND1 is a weak oncogene and it was expected that, like c-erbB-2, over-expression of cyclin D1 protein would be associated with a poor prognosis. Early immunohistochemical prognostic studies produced equivocal results but we, and others, have recently shown that strong staining for cyclin D1 is more likely to be seen in well differentiated, estrogen receptor positive carcinomas. Furthermore, we have found that over-expression of cyclin D1 is actually associated with a good outcome, both in terms of prognosis and response to endocrine treatment. Cyclin D1 is frequently over-expressed in ductal carcinoma in situ but not in benign breast disease, including atypical ductal hyperplasia; hence its expression appears to be closely linked with carcinogenesis. In order to help explain the apparent beneficial effects of cyclin D1 over-expression, a number of closely associated cell cycle proteins have also been evaluated, including the cyclin dependent kinase inhibitor p27, which blocks the activating effects of cyclin D1. Initial reports show that high levels of p27 are associated with a good prognosis and we have shown a positive association between p27 and cyclin D1 expression. These clinical results of cyclin D1 are an example of how information obtained from basic cell biology studies needs to be complemented by clinical studies to ascertain the true worth of a prognostic marker.