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:2/2/2016)... YORK , Feb. 2, 2016 ... of the bioinformatic market by reviewing the recent ... enabled tools that drive the field forward. Includes ... to: Identify the challenges and opportunities that ... providers and software solution developers, as well as ...
(Date:2/2/2016)... Va. , Feb. 2, 2016   ... award from the U.S. Army Research Office and ... the range and sensitivity of the company,s ... Past Accounting Mission and, more generally, defense-related DNA ... DNA phenotyping capabilities (predicting appearance and ancestry from ...
(Date:2/1/2016)... YORK , Feb. 1, 2016  Today, the ... Association (AHA) announced plans to develop a first of ... computing power of IBM Watson. In the first application ... AHA, IBM (NYSE: IBM ), and Welltok will ... and health assessments with cognitive analytics, delivered on Welltok,s ...
Breaking Biology News(10 mins):
(Date:2/8/2016)...  NanoViricides, Inc. (NYSE MKT: NNVC) (the "Company"), a nanomedicine company ... MD, MPH, will present information about the company,s programs at the ... New York City . --> ... at 5:30PM EST. Registered attendees can request a one on one ... . --> New York City . ...
(Date:2/6/2016)... ... February 06, 2016 , ... Contact:, Abby ... for Excellence in Education Sponsors Teacher Training Program , Bite of Science Dinner ... The Center for Excellence in Education (CEE) will sponsor a Bite of Science ...
(Date:2/5/2016)... -- Australian-US drug discovery and development company, Novogen Limited (ASX:NRT; ... new Chairman, Mr John O,Connor , and new Deputy ... James Garner , has also been formally appointed to ... Mr Iain Ross , will resume his role on ... Garner , has also been formally appointed to the Board ...
(Date:2/4/2016)... Falls Church, VA (PRWEB) , ... ... ... a first-year cybersecurity conference presented by Bloomsburg University’s Digital Forensics Club, takes ... Bloomsburg, PA. The two-day event features 20+ speakers and activities such as ...
Breaking Biology Technology: