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

Lung Cancer. 2007 Jan;55(1):1-14. doi: 10.1016/j.lungcan.2006.09.024. Epub 2006 Oct 27.


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Methods: Data published until June 2006 are summarized, and previously unpublished results from our own research are included.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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoma / pathology
  • Adenoma / physiopathology
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / physiopathology*
  • Cell Transformation, Neoplastic
  • Cyclin D1 / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / pathology
  • Glioblastoma / physiopathology
  • Humans
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / physiopathology*
  • Polymorphism, Genetic


  • Cyclin D1