DNA “marks” gastric cancer risk
Infection with the stomach-dwelling bacterium Helicobacter pylori is a strong risk factor for gastric cancer. But since about half of the world’s population is infected, and less than 1 percent of infected individuals develop cancer, other factors must contribute to gastric cancer risk.
Barbara Schneider, Ph.D., and colleagues are examining the role of epigenetic factors – modifications that alter gene expression, but do not affect the primary DNA sequence. They compared gastric biopsies from two Colombian populations – one with high risk of gastric cancer and one with lower risk – with similar prevalence of H. pylori infection.
In the Dec. 1 International Journal of Cancer, they report that regulatory regions (promoters) of two genes (RPRM and TWIST1) were more heavily modified (methylated) in the high-risk population compared to the low-risk population. Infection with more virulent bacterial strains was also associated with increased DNA methylation. The results suggest that DNA methylation could be a useful biomarker for determining gastric cancer risk.
— Melissa Marino
Detour around the estrogen receptor
iStockphoto.com
A multi-institutional team of researchers has now identified a potential new target for treating these tumors. The study, led by Ann Richmond, Ph.D., and colleagues at Tulane University, shows that increased expression of a “chemokine” receptor, CXCR4, allows estrogen-dependent breast tumors to grow independently of estrogen.
In human tumor samples, they show that increased expression of CXCR4 is correlated with poorer prognosis and decreased patient survival, regardless of ER status. They further show that inhibiting CXCR4 in a mouse model of breast cancer can reverse tumor growth and metastasis.
The results, reported in the Jan. 15 issue of Cancer Research, suggest that CXCR4 signaling is a rational target for the treatment of breast cancers that have become resistant to hormone therapies.
— Melissa Marino
Spicing up cancer prevention
Curcumin – the active ingredient that flavors curries and gives the Indian spice turmeric its yellow color – is being studied for its ability to prevent tumor development. Its efficacy, however, is limited by chemical and metabolic instability. Previous studies have focused on the non-enzymatic (not mediated by a protein) cleavage of curcumin into smaller fragments.
iStockphoto.com
Journal of Biological Chemistry
They also found that the pathway generates an intermediate compound – a reactive chemical called a quinone methide. Because anti-cancer drugs with chemical components (phenol rings) like curcumin work by forming quinone methides, the findings suggest that the oxidative transformation of curcumin may contribute to its cancer-preventing activity.
— Leigh MacMillan
Brain may complicate pancreas studies
Conditional gene targeting – deleting or altering a gene in a specific tissue or at a specific time – is a powerful tool for probing gene function in vivo. It has been extensively used to study the biology of the pancreas and its insulin-producing beta cells.
Three laboratories at Vanderbilt, in collaboration with groups at the University of Chicago and the University of Michigan, studied expression of a targeting tool called “Cre” in genetically altered mouse lines used for beta cell- or pancreas-specific targeting. They found that when parts of the insulin or Pdx genes were used to “drive” Cre expression in the beta cells or pancreas, it was also surprisingly expressed in the brain. The researchers found Cre in nutrient-sensing neurons involved in glucose balance, appetite, weight, and energy expenditure – neurons whose activities might confound studies of beta cell biology.
The researchers suggest in the December issue of the journal Diabetes that studies using Cre-expressing mouse models need to be interpreted carefully to assess whether results can be attributed solely to the beta cells or pancreas.
— Leigh MacMillan
We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.
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