A Possible Role Of GDDR In The Development Of Helicobacter Pylori-associated Gastric Cancer

【Objectives】GDDR(gastric dramatic down-related gene) had been cloned for the first time by usin2002by suppression subtractive hybridization(SSH). The protein GDDR is frequentlydown-regulated or lost in gastric carcinoma. Although we know about the molecularstructure, location on the chromosome and the expression of GDDR, the role of GDDRand its molecular mechanism remain unclear. Helicobacter pylori(H.pylori) has beendeemed to a significant risk factor for gastric cancer. Some studies implied that H.pyloricould regulate the expression of GDDR. Therefore, the aims of this study are toinvestigate the clinicopathologic significance of GDDR in precancerous lesions andgastric cancer associated with H.pylori and to explore the possible molecular mechanismof H.pylori-induced the change of GDDR expression in the development of gastriccarcinoma.【Methods】1. GDDR expression and subcellular localization were examined and evaluated byImmunohistochemistry(IHC) in a set of patient tissues.2. IHC, Co-culture assay, Immunofluorescence staining, qRT-PCR and Western blot analysis were used to detect the expression level of GDDR with or withoutH.pylori-infection status.3. To further explore the negative role of GDDR in tumor growth in vivo, weexplored it by injecting cells into nude mice.【Results】1. The expression of GDDR significantly decreased in the development of gastriccancer as compared with normal controls.2. IHC, Western blot and qRT-PCR provided more detailed evidence that GDDR wasdown-regulated with H.pylori-infection. Western blot and Immunofluorescence stainingshowed that the NF-κB signaling pathway may be involved in H.pylori-downregulatedGDDR expression in human gastric cancer.3. Plate colony formation assay and MTT showed that GDDR inhibited the clone andproliferation of gastric cancer cells.4. After H.pylori eradication, the expression of GDDR was up-regulated obviously.【conclusion】In conclusion, our data provide the first evidence that the gradually down-regulatedexpression of GDDR is an early molecular event in the development of gastric cancer.NF-κB signaling pathway is involved in H.pylori-downregulated GDDR expression.GDDR may play an important role in the early diagnosis of gastric cancer and may beutilized as a molecular diagnostic marker and a new target of anti-tumor moleculartherapy.