CYCLIN D1 AND HUMAN NEOPLASIA

Neoplasia is characterised by abnormal regulation of the cell cycle. C yclin D1 is a protein derived from the PRAD1, CCND1 or bc1-1 gene on c hromosome 11q13, which is involved in both normal regulation of the ce ll cycle and neoplasia. In the G(1) (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 phosphor ylating the product of the retinoblastoma gene (pRB), which then relea ses transcription factors important in the initiation of DNA replicati on. Amplification of the CCND1 gene or overexpression of the cyclin D1 protein releases a cell from its normal controls and causes transform ation to a malignant phenotype. Analysis of these changes provides imp ortant diagnostic information in mantle cell (and related) lymphomas, and is of prognostic value in many cancers. Knowledge of cyclin D1's r ole in malignancy at the various sites, provides a basis on which futu re treatment directed against this molecule can proceed.