Abstract
The incidence of esophageal adenocarcinoma, as one of a few human cancers, has been increasing recently in the United States. Tobacco smoke and low fruit and vegetable consumption are risk factors for both esophageal squamous cell carcinoma and adenocarcinoma, whereas frequent gastroesophageal reflux, overweight, and obesity are linked to the increased incidence of esophageal adenocarcinoma. Our research objective is to understand the molecular mechanisms of esophageal carcinogenesis for developing strategies in its early detection and prevention. In our previous studies, we have associated some of these risk factors with altered gene expression in esophageal cancer. We found that benzo[a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke and environmental pollution) and bile acid (a tumor promoter in gastrointestinal cancer) suppressed expression of RAR‐β2 and RRIG1, but induced EGFR, p‐ERK, AP‐1, and COX‐2 expression in esophageal cancer cells. In this study, we have detected expression of FXR and NHE‐1, a regulator of intracellular pH, in esophageal cancer tissue specimens and then determined effects of their inhibitors in suppressing growth of esophageal cancer cells. We found that expression of FXR and NHE‐1 is increased in esophageal cancer compared to the normal tissues. We also found that inhibition of FXR and NHE‐1 activity by using guggulsterone and amiloride can effectively suppress the tumor cell growth and gene expression. Further study will reveal the underlying molecular mechanisms and use FXR and NHE‐1 expression as biomarkers for early detection or prognosis of esophageal cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A55.
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