The molecular mechanisms that may underlie the ability of the tumor suppressor gene Rb2/p130 to block progression of non-small cell lung cancer have been identified for the first time, according to an article in the October 9th issue of Oncogene.

The study, led by Antonio Giordano, M.D., Ph.D., was a follow-up to previous experiments by the same American group that demonstrated an inverse relationship between expression of the gene Rb2 and the aggressiveness of lung cancer tumors. In those earlier studies, normal alleles of Rb2 were introduced into mice with lung tumors using a viral system. When the Rb2 gene was overexpressed in the cancer cells, it caused the tumors in the mice to regress completely.

“In this study, we wanted to understand the molecular mechanisms behind Rb2/p130 tumor growth inhibition,” said Giuseppe Russo, Ph.D., the lead author. “We wanted to know what this gene does in lung cancer cells, what other genes it may target, and how it controls cell regulation. It’s like this molecular process of tumor regression is a movie and Rb2 is the lead actor. What we wanted to know is who the supporting cast is.”

After introducing normal alleles of Rb2 into H23 lung cancer cells via a viral shuttle, the researchers used customized microarray analysis to examine the simultaneous expression of thousands of genes within the cancer cell.

“Through the use of the microarray, we were able to see which genes were overexpressed or underexpressed because of the enhanced Rb2 gene expression,” said Giordano. “This is the first time that we have been able to clearly identify the genes that were being regulated by the Rb2 expression in lung cancer cells.”

Some of the nearly 70 regulated genes that were identified through the current study were previously known to be involved in the progression of lung cancer, said Giordano, which means the researchers were able to confirm previously published data. “But many of the identified genes were not previously known to be involved in lung cancer or be regulated by Rb2,” he added.

The researchers believe that identifying these genes, especially those not previously known to play a role in cancer progression, could play an important role in developing future gene therapies to diagnose and treat lung cancer.