Gene linked to aggressive progression of liver cancer identified

February 18th, 2009 - 2:21 pm ICT by ANI  

Washington, Feb 18 (ANI): Researchers at Virginia Commonwealth University have identified a gene that plays key role in regulating liver cancer progression.

According to researchers, the discovery could one day lead to new-targeted therapeutic strategies to fight the highly aggressive disease.

In the study, researchers found that the astrocyte elevated gene-1, AEG-1, plays a key role in regulating Hepatocellular carcinoma, HCC, or liver cancer in series of cellular models.

By examining human liver tumour cells of patients with HCC, the team found that the expression of AEG-1 gradually increases as the tumour becomes more and more aggressive.

Using microarray technology, they analyzed cDNA from the tumour cells and determined that AEG-1 modulates expression of genes relevant to the progression of HCC, including invasion, metastasis, resistance to chemotherapy, the formation of new blood vessels, and senescence. cDNAs are complementary DNAs that are generated from mRNAs to analyze gene expression profiles.

AEG-1 also activates multiple intracellular signaling pathways that are known to be involved in HCC progression. So, strategies to inhibit AEG-1 that could lead to the shutdown of these pathways, either by small molecules or by siRNAs, might be an important therapeutic modality for HCC patients, said principal investigator Devanand Sarkar, Ph.D., MBBS, assistant professor in the Department of Human and Molecular Genetics in the VCU School of Medicine, and Harrison Endowed Scholar in Cancer Research at the VCU Massey Cancer Center.

Sarkar said that siRNAs are small inhibitory RNAs that can specifically inhibit targeted mRNA and protein production. siRNAs may be used in the future for targeted inhibition of AEG-1 in patients.

According to Sarkar, the team found a significantly higher expression of AEG-1 protein in more than 90 percent of tumour samples from HCC patients compared to normal human liver cells.

The expression of AEG-1 protein gradually increases as the disease becomes more aggressive. No other genes have been shown to be upregulated in such a high percentage of HCC patients, said Sarkar.

Further, he said that findings from a separate pool of 132 HCC patients revealed significant overexpression of AEG-1 mRNA compared to normal liver. In a subset of these patients, the team detected an increased number of copies of the AEG-1 gene.

We observed an increase in AEG-1 DNA, mRNA and protein in HCC patients, which indicates a significant involvement of AEG-1 in HCC progression. Stable over expression of AEG-1 converts non-tumourigenic human HCC cells into highly aggressive vascular tumours and inhibition of AEG-1 abrogates tumourigenesis by aggressive HCC cells, he said.

The study is published online in the February issue of the Journal of Clinical Investigation. (ANI)

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