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Cyclin D1 in breast cancer
Author(s): Barnes DM, Gillett CE
Source: BREAST CANCER RESEARCH AND TREATMENT    Volume: 52    Issue: 1-3    Pages: 1-15    Published: 1998  
Times Cited: 127     References: 69     
Abstract: 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.
Document Type: Article
Language: English
Reprint Address: Barnes, DM (reprint author), Guys Hosp, Hedley Atkins ICRF Breast Pathol Lab, 3rd Floor,Thomas Guy House, London SE1 9RT, England
Addresses:
1. Guys Hosp, Hedley Atkins ICRF Breast Pathol Lab, London SE1 9RT, England
Publisher: KLUWER ACADEMIC PUBL, SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
Subject Category: Oncology
IDS Number: 169MR
ISSN: 0167-6806
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