细胞周期蛋白D1与人类肿瘤
Cyclin D1 and human neoplasia.
作者信息
Donnellan R, Chetty R
机构信息
Department of Pathology, University of Natal Medical School, Durban, South Africa.
出版信息
Mol Pathol. 1998 Feb;51(1):1-7. doi: 10.1136/mp.51.1.1.
Neoplasia is characterised by abnormal regulation of the cell cycle. Cyclin D1 is a protein derived from the PRAD1, CCND1 or bcl-1 gene on chromosome 11q13, which is involved in both normal regulation of the cell cycle and neoplasia. In the G1 (resting) phase of the cell cycle, cyclin D1 together with its cyclin dependent kinase (cdk) partner, is responsible for transition to the S (DNA synthesis) phase by phosphorylating the product of the retinoblastoma gene (pRB), which then releases transcription factors important in the initiation of DNA replication. Amplification of the CCND1 gene or overexpression of the cyclin D1 protein releases a cell from its normal controls and causes transformation to a malignant phenotype. Analysis of these changes provides important diagnostic information in mantle cell (and related) lymphomas, and is of prognostic value in many cancers. Knowledge of cyclin D1's role in malignancy at the various sites, provides a basis on which future treatment directed against this molecule can proceed.
肿瘤形成的特征是细胞周期的异常调控。细胞周期蛋白D1是一种由位于11q13染色体上的PRAD1、CCND1或bcl-1基因衍生而来的蛋白质，它既参与细胞周期的正常调控，也与肿瘤形成有关。在细胞周期的G1（静止）期，细胞周期蛋白D1与其细胞周期蛋白依赖性激酶（cdk）伙伴一起，通过磷酸化视网膜母细胞瘤基因（pRB）的产物，负责向S（DNA合成）期的转变，然后pRB释放对DNA复制起始很重要的转录因子。CCND1基因的扩增或细胞周期蛋白D1蛋白的过度表达使细胞脱离其正常控制，并导致向恶性表型的转变。对这些变化的分析为套细胞（及相关）淋巴瘤提供了重要的诊断信息，并且在许多癌症中具有预后价值。了解细胞周期蛋白D1在各个部位恶性肿瘤中的作用，为未来针对该分子的治疗提供了依据。
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