Navigation Links
Researchers identify gene linked to aggressive progression of liver cancer

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
Virginia Commonwealth University

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:
(Date:6/9/2016)... June 9, 2016 Paris ... Teleste,s video security solution to ensure the safety of people ... during the major tournament Teleste, an international ... and services, announced today that its video security solution will ... to back up public safety across the country. The system ...
(Date:6/2/2016)... June 2, 2016 Perimeter Surveillance ... Unmanned Systems, Physical Infrastructure, Support & Other Service  ... visiongain offers comprehensive analysis of the global ... will generate revenues of $17.98 billion in 2016. ... Inc, a leader in software and hardware technologies for ...
(Date:5/12/2016)... May 12, 2016 , a ... the overview results from the Q1 wave of its ... wave was consumers, receptivity to a program where they ... a health insurance company. "We were surprised ... says Michael LaColla , CEO of Troubadour Research, ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... 2016 Epic Sciences unveiled a liquid ... to PARP inhibitors by targeting homologous recombination deficiency ... new test has already been incorporated into numerous ... types. Over 230 clinical trials are ... including PARP, ATM, ATR, DNA-PK and WEE-1. Drugs ...
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica ... in people with peritoneal or pleural mesothelioma. Their findings are the subject of a ... , Diagnostic biomarkers are signposts in the blood, lung fluid or tissue of ...
(Date:6/23/2016)... ... 2016 , ... UAS LifeSciences, one of the leading manufacturers ... Probiotics, into Target stores nationwide. The company, which has been manufacturing high quality ... list of well-respected retailers. This list includes such fine stores as Whole Foods, ...
(Date:6/23/2016)... , June 23, 2016 /PRNewswire/ - FACIT has ... Ontario biotechnology company, Propellon Therapeutics Inc. ... and commercialization of a portfolio of first-in-class WDR5 ... targets such as WDR5 represent an exciting class ... in precision medicine for cancer patients. Substantial advances ...
Breaking Biology Technology: