By Penny Stern, MD

NEW YORK (Reuters Health) - A mechanism responsible for turning off a tumor-suppressing gene in many lung cancers has been described by an international team of researchers.

Dr. Adi F. Gazdar of the University of Texas Southwestern Medical School in Dallas, together with colleagues there and in Italy, Australia and the Netherlands, reports on the findings in the August issue of the Journal of the National Cancer Institute.

Gazdar explained to Reuters Health that ``it is obvious...cells need to inactivate many genes before they can become malignant.'' In the case of lung cancer, scientists have long known that retinoic acid plays a role in this process.

``We have known that (retinoic acid receptor-beta) is downregulated in lung cancers and in the bronchial (lining cells) of smokers, although the mechanism was not understood,'' Gazdar said.

He added that trials using retinoids as a lung cancer preventive agent have been unsuccessful.

In the current work, Gazdar and his team have ``demonstrat(ed) the mechanism of inactivation'' that shuts down a gene that would normally work to suppress tumor formation, he said.

Specifically, the retinoic acid receptor-beta (RAR-beta) gene is methylated. Methyls are chemical groups made up of one carbon atom attached to three hydrogen atoms. When the RAR-beta gene is methylated, the gene's normal expression is prevented.

And, not only is RAR-beta important in development lung cancer, ``the RAR-beta is also frequently methylated in breast cancers,'' Gazdar pointed out.

According to the researcher, ``we are learning that aberrant methylation of gene promotors is a frequent method of shutting off gene expression.'' Also, he said, ``it can be reversed after exposure to a demethylating agent.''

As to the therapeutic implications of these findings, Gazdar suggested that ``if the methylation can be removed, that by itself may be useful. Or, the combination of demethylation and a retinoid may be more effective, as has been shown for some breast cancers cell lines by (laboratory) experiments.''

While Gazdar would not specify when practical applications might arise from these findings, he did comment that ``new therapeutic and chemopreventive approaches are being developed and will be tested in the near future.''

(From Yahoo)