Navigation Links
Researchers identify gene linked to aggressive progression of liver cancer
Date:2/17/2009

RICHMOND, Va. (Feb. 17, 2009) Virginia Commonwealth University researchers have identified a gene that plays a key role in regulating liver cancer progression, a discovery that could one day lead to new targeted therapeutic strategies to fight the highly aggressive disease.

Hepatocellular carcinoma, HCC, or liver cancer, is the fifth most common cancer and the third leading cause of cancer deaths in the world. Treatment options for HCC include chemotherapy, chemoembolization, ablation and proton-beam therapy. Liver transplantation offers the best chance for a cure in patients with small tumors and significant associated liver disease.

In the study, published online in the February issue of the Journal of Clinical Investigation, researchers reported that the astrocyte elevated gene-1, AEG-1, plays a key role in regulating HCC in series of cellular models. By examining human liver tumor cells of patients with HCC, the team found that the expression of AEG-1 gradually increases as the tumor becomes more and more aggressive. Using microarray technology, they analyzed cDNA from the tumor 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.

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, Sarkar said.

According to Sarkar, the team found a significantly higher expression of AEG-1 protein in more than 90 percent of tumor 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 overexpression of AEG-1 converts non-tumorigenic human HCC cells into highly aggressive vascular tumors and inhibition of AEG-1 abrogates tumorigenesis by aggressive HCC cells," he said.

Previous studies suggest that the expression of AEG-1 is very low in normal cells or tissues such as breast, prostate and brain. However, in cancers of the same organs, expression of AEG-1 is significantly increased.

The team will conduct studies to further understand the molecular mechanisms by which AEG-1 works and identify other proteins with which it interacts.


'/>"/>

Contact: Sathya Achia Abraham
sbachia@vcu.edu
804-827-0890
Virginia Commonwealth University
Source:Eurekalert

Related biology news :

1. Case Western Reserve researchers looking at light-induced toxins in air and water
2. McMaster researchers discover new mode of how diseases evolve
3. Researchers shed new light on connection between brain and loneliness
4. Texas researchers provide emissions data for livestock industry
5. Biodiversity itself begets a species cascade, researchers say
6. NYU Langone Medical Center researchers find micro RNA plays a key role in melanoma metastasis
7. While focusing on heart disease, researchers discover new tactic against fatal muscular dystrophy
8. NSF-funded workshops help young researchers teach science
9. Researchers observe evolution chain reaction
10. Researchers examine role of climate change in disease spread
11. Mayo Clinic researchers suspect a novel gene is causing restless legs syndrome in a large family
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/13/2017)... April 13, 2017 According to a new market ... Identity Analytics, Identity Administration, and Authorization), Service, Authentication Type, Deployment Mode, Vertical, ... Market is expected to grow from USD 14.30 Billion in 2017 to ... of 17.3%. ... MarketsandMarkets Logo ...
(Date:4/11/2017)... Apr. 11, 2017 Research and Markets has ... report to their offering. ... The global eye tracking market to grow at a CAGR of ... Eye Tracking Market 2017-2021, has been prepared based on an in-depth ... market landscape and its growth prospects over the coming years. The ...
(Date:4/11/2017)... , April 11, 2017 NXT-ID, ... security technology company, announces the appointment of independent Directors Mr. ... to its Board of Directors, furthering the company,s corporate ... ... NXT-ID, we look forward to their guidance and benefiting from ...
Breaking Biology News(10 mins):
(Date:8/10/2017)... ... August 09, 2017 , ... The ... the clinic is here. The team at Capricor Therapeutics, Inc. utilized a cardiosphere-derived ... clinical studies. , Dr. Travis Antes, head of analytical development at Capricor ...
(Date:8/10/2017)... ... August 09, 2017 , ... Okyanos Center for Regenerative Medicine ... the Pelican Bay Hotel in Freeport, Grand Bahama on September 27, 2017. This daytime ... , With oversight from the Ministry of Health’s National Stem Cell Ethics Committee (NSCEC) ...
(Date:8/10/2017)... ... August 10, 2017 , ... DrugDev and the ... to demonstrate how Good Clinical Practice (GCP) can be used throughout the site ... webinar will discuss the importance of GCP compliance, how sites are affected by GCP ...
(Date:8/10/2017)... (PRWEB) , ... August 10, 2017 , ... ... the stock market news outlet had initiated coverage on Next Group Holdings, Inc. ... and underserved consumer markets geared toward those that cannot engage in traditional banking ...
Breaking Biology Technology: