Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation

Gautschi, Oliver; Ratschiller, Daniel; Gugger, Mathias; Betticher, Daniel C; Heighway, Jim (2007). Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung cancer, 55(1), pp. 1-14. Amsterdam: Elsevier 10.1016/j.lungcan.2006.09.024

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PURPOSE: To review the evidence implicating the deregulation of cyclin D1 in the pathogenesis of non-small cell lung cancer (NSCLC), and to discuss the opportunities for targeted clinical intervention. METHODS: Data published until June 2006 are summarized, and previously unpublished results from our own research are included. RESULTS: In normal cells, cyclin D1 complexes with and activates cyclin-dependent kinases (CDK) and acts as a transcriptional regulator. The protein is frequently overexpressed in a wide range of cancers, sometimes coincident with CCND1 (cyclin D1) gene amplification (5-20% of tumours). A low level of somatic mutations have been seen in certain tumours. CCND1 is amplified in NSCLC and cyclin D1 is frequently overexpressed in tumours and pre-invasive bronchial lesions, generally from one parental allele. Mutation analyses revealed a frequent CCND1 gene polymorphism (A870G) that modulates alternative splicing and allows expression of an alternative cyclin D1 transcript (transcript cyclin D1b). The encoded cyclin D1b protein lacks a specific phosphorylation site required for nuclear export. Genotype has been correlated with the risk and/or severity of disease or drug response across a range of malignancies, including lung cancer. Together, these findings suggest a strong pathological role for cyclin D1 deregulation in bronchial neoplasia. CONCLUSION: Current data indicate that cyclin D1 overexpression is not a consequence of, but rather a pivotal element in the process of malignant transformation in the lung and other tissues. This understanding may open new avenues for lung cancer diagnosis, treatment and prevention.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Gautschi, Oliver; Ratschiller, Daniel and Gugger, Mathias

ISSN:

0169-5002

ISBN:

17070615

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:46

Last Modified:

17 Mar 2015 21:45

Publisher DOI:

10.1016/j.lungcan.2006.09.024

PubMed ID:

17070615

Web of Science ID:

000244103200001

URI:

https://boris.unibe.ch/id/eprint/19007 (FactScience: 1372)

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