Failure of Tumor Suppressor Gene Promotes Lung Cancer Development

A team of British and American cancer researchers has identified a tumor suppressor gene (TSG) that fails to function in both small and non-small cell lung cancers.

Investigators at the University of Nottingham (United Kingdom) and at the Washington University School of Medicine (St. Louis, MO, USA) recently published two papers characterizing a gene that functions in normal lung tissue but is down regulated in lung tumors. The gene, known as LIM domain containing protein 1 (LIMD1), is located on chromosome 3p21.3.

In the first study, published in the November 15, 2008, edition of the International Journal of Cancer, the investigators used an anti-LIMD1 specific monoclonal antibody to investigate expression/localizations of the LIMD1 protein in a well-characterized tissue microarray of breast cancers and normal adjacent epithelial tissue. Results showed that LIMD1 expression was much higher in normal tissue. The location of LIMD1 activity was also found to be important. Nuclear LIMD1 activity was associated with normal tissue and less aggressive tumors, while cytoplasmic LIMD1 activity was linked to aggressive tumors.

The second paper, published in the December 5, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS), confirmed that LIMD1 was a bona fide TSG. Mice that were genetically engineered to lack LIMD1 were found to be predisposed to chemical-induced lung adenocarcinoma. Genetic inactivation of LIMD1 in mice heterozygous for the oncogenic K-RasG12D gene markedly increased tumor initiation, promotion, and mortality.

These studies, which were supported by a grant from the British Lung Foundation, may lead to possible new treatments and early screening techniques for lung cancer.

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University of Nottingham
Washington University School of Medicine