Scientists Isolate Suppressor Gene as Potential Drug Target

Scientists have found an unusual lung-cancer tumour-suppressor gene, which was shown to restore the inactivated gene slowing the growth of tumour cells.

Its importance in cancers of the lung and head and neck may make it a viable drug target.

The findings might therefore lead to new strategies for the treatment and early detection of lung cancer. The study could also lead to a better understanding of the molecular changes that occur in tumour cells during lung-cancer progression.

Researchers at The Ohio State University Comprehensive Cancer Centre in collaboration with the Arthur James Cancer Hospital and Richard Solove Research Institute, Christoph Plass, a professor of molecular virology, immunology and medical genetics and a researcher in the OSU Human Cancer Genetics Program, scanned the same chromosome region using a technology known as restriction landmark genome scanning, which identifies methylated genes.

The researchers examined the region in about 50 tumour samples from patients with head and neck squamous-cell carcinomas and with non-small-cell lung cancer, which is responsible for about 85 per cent of lung cancer cases.

From this, they identified TCF21 as a gene often silenced by methylation compared with normal airway cells.

TCF21 is silenced in tumour cells through a chemical change known as DNA methylation, a process that is potentially reversible.

"A picture is emerging that certain genes tend to be silenced mainly by DNA methylation, while others tend to be silenced by genetic mutations," Plass commented. "This gene seems to be silenced by DNA methylation."

Through a series of experiments, Plass and his colleagues showed that an active TCF21 gene could be silenced by DNA methylation.

First author Laura Smith, a postdoctoral fellow in Plass' laboratory, said that because this gene is silenced by DNA methylation, it might be possible to reactivate it using drugs that reverse the methylation process.

"This could provide a new strategy for treating these cancers," she said.

The researchers also used a lung-cancer cell line to show that if the active version of the TCF21 gene is placed in tumour cells, the active gene will slow the cells' growth rate.

Lastly, the researchers showed that mice injected with lung-tumour cells that had an active TCF21 gene developed tumours that were two to three times smaller than tumours that developed from cancer cells with a silent TCF21 gene.

The study was published online in the Jan. 13 early edition of the Proceedings of the National Academy of Sciences.