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Epigenetic Activity Silences Tumor Suppressing Gene In Lung Cancer

September 19, 2005
Temple University
The attaching of methyl--or chemical--groups onto DNA sequences within the tumor suppressing gene Rb2/p130 can cause the gene to cease functioning in non-small lung cancer cells (NSLC) and retinoblastoma cells.

Antonio Giordano, M.D., Ph.D. (right), Director of the Sbarro Institute for Cancer Research and Molecular Medicine in the College of Science and Technology at Temple University, and post Research Fellow Marcella Macaluso perform electrophoresis on DNA samples extracted from human tissue that have been placed in agarose gel. Agarose gel electrophoresis of DNA is the first step in doing Rb2/p130 diagnostic tests for breast, lung and other cancer. Giordano discovered Rb2/p130, a tumor suppressor gene, while a researcher at Temple’s Fels Institute for Cancer Research and Molecular Biology in the early 1990s.
Credit: Image courtesy of Temple University

Their findings are reportedin two studies: "Tumor-specific exon 1 mutations could be the 'hitevent' predisposing Rb2/p130 gene to epigenetic silencing in lungcancer" and "Genetic and epigenetic alterations of RB2/p130 tumorsuppressor gene in human sporadic retinoblastoma: implications forpathogenesis and therapeutic approach," both of which appear inSeptember issues of Oncogene (www.nature.com/onc).

The jointstudies at Temple and Siena were coordinated by Antonio Giordano, M.D.,Ph.D., director of Sbarro Institute at Temple (www.shro.org), and byMarcella Macaluso of the Sbarro Institute and Caterina Cinti of bothCentro Nazionale Ricerche and the University of Siena.

Giordanosaid that the researchers were puzzled when they found Rb2/130, thetumor suppressing gene discovered by Giordano in the early 1990s, in anepigenetic state in both the NSLC and retinoblastoma cells. In thisepigenetic state, the gene showed no signs of mutation, but is silentin its expression or function.

Further examination of the genefound that it had been methylated, a process in which methyl orchemical groups attached themselves to the gene, attacking a sequenceof the Rb2/p130's DNA and thus causing it to cease functioning.

"Thesestudies are providing very important information on how cancerous andpre-cancerous conditions can be detected by the presence of themethylated state of Rb2/p130," said Giordano. "These cancerous orpre-cancerous conditions can be treated with drugs or agents thatde-methylate the Rb2/p130 gene. Once the drugs or agents disconnect themethyl groups from Rb2/p130, the gene begins to again express itself orfunction normally."

He likened this methylation/de-methylationphenomenon--which can stop or start the expression of a gene--to alightswitch which is used to turn a lamp off or on.

Giordano saidsome of these agents that will de-methylate Rb2 are already available,but have not been previously used because researchers did not know thatthe lack of expression from the gene was being caused by itsmethylation.

"Our discovery is providing a smart method toidentify novel methylated drugs or agents that can assist in restartingthe vital expression of Rb2/p130," he said.

Through the use of asimple genetic (both at DNA and Protein level) test of Rb2 gene andprotein from a human tissue sample, said Giordano, scientists coulddetermine if cancerous or pre-cancerous conditions exist because of theepigenetic state of the gene.

"We could develop a potential test which could save many, many people from the ravages of cancer," he said.

Story Source:

The above story is based on materials provided by Temple University. Note: Materials may be edited for content and length.

Cite This Page:

Temple University. "Epigenetic Activity Silences Tumor Suppressing Gene In Lung Cancer." ScienceDaily. ScienceDaily, 19 September 2005. <www.sciencedaily.com/releases/2005/09/050919082603.htm>.
Temple University. (2005, September 19). Epigenetic Activity Silences Tumor Suppressing Gene In Lung Cancer. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2005/09/050919082603.htm
Temple University. "Epigenetic Activity Silences Tumor Suppressing Gene In Lung Cancer." ScienceDaily. www.sciencedaily.com/releases/2005/09/050919082603.htm (accessed July 30, 2014).

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