Gastric cancer is the fourth most common form of incident cancer and the second most common cause of cancer death in the world. This malignancy is considered to be poorly treatable, and the surgery that is the mainstay of current treatment carries significant morbidity and mortality. To better treat and prevent this disease, it is important to understand factors that affect its development. p53 tumor suppressor is among the cellular factors that play an important role in the prevention of gastric tumors. Although the p53 protein has been relatively well characterized, less is known about other members of the p53 family, p73 and p63. Accumulating evidence suggest that p73 and p63 significantly affect the p53 activity and function in concert with p53 in regulation of tumorigenesis. Our data suggest that p73 plays an important role in the interaction of gastric epithelial cells with H. pylori, a Gram-negative bacterial pathogen that is a prominent risk factor for the development of gastric cancer.
We aim to delineate the role of the p53 protein family in the development of gastric tumor using mouse models and other in vitro and in vivo approaches. These comprehensive studies may provide new avenues for the development of novel prognostic and therapeutic targets.

Public Health Relevance

Gastric cancer is the second most common cause of cancer death in the world. Despite recent advances in treatment of this disease, gastric cancer remains to be a serious health problem. Our research analysis may provide valuable information on the mechanisms of development of this disease and its potential treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA138833-03
Application #
8209272
Study Section
Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
Program Officer
Daschner, Phillip J
Project Start
2010-08-01
Project End
2015-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
3
Fiscal Year
2012
Total Cost
$349,658
Indirect Cost
$125,518
Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Peng, DunFa; Hu, TianLing; Soutto, Mohammed et al. (2014) Glutathione peroxidase 7 has potential tumour suppressor functions that are silenced by location-specific methylation in oesophageal adenocarcinoma. Gut 63:540-51
Zaika, Elena; Bhardwaj, Vikas; Wei, Jinxiong et al. (2013) Proinflammatory cytokines and bile acids upregulate ?Np73 protein, an inhibitor of p53 and p73 tumor suppressors. PLoS One 8:e64306
Zaika, Elena; Wei, Jinxiong; Yin, Dengping et al. (2011) p73 protein regulates DNA damage repair. FASEB J 25:4406-14
Wei, Jinxiong; Nagy, Toni A; Vilgelm, Anna et al. (2010) Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterology 139:1333-43