Elucidating Regulatory Pathway of Estrogen Receptors in Helicobacter pylori-infected Gastric Cancer
Date Issued
2011
Date
2011
Author(s)
Hu, Po-Yu
Abstract
This study is to elucidate the regulatory mechanism of estrogen receptors in Helicobacter pylori (H. pylori)-infected Gastric cancer. The correlation between H. pylori infection and gastric cancer was first analyzed using the cDNA microarray data from 8 gastric cancer patients. Among the differentially expressed H. pylori-related genes, 82 were found to be up-regulated two-fold. Ingenuity Pathway Analysis (IPA) analysis showed these genes to be highly related to four pathways with cancer progression, where estrogen receptor (ER) was the crucial hub in the network, and regulating 20 cancer related genes. A total of 14 ER-related genes were confirmed by q-RT-PCR to be up-regulated 1.5-fold in H. pylori-infected human AGS cells. Moreover, we utilized a human genome-wide high-affinity ERE database and built a new regulatory pathway for H. pylori-infected gastric cancer. Further experimental analysis included MTT assay, cell cycle analysis, oxidative stress resistance analysis, invasion assay, western blot, and q-RT-PCR. Our results show that either 1 nM estradiol or 10-5 M fulvestrant can reduce AGS viability, oxidative resistance, and metastasis that were increased by H. pylori infection. H. pylori enhanced the growth, resistance, and metastasis abilities of gastric cancer cells through ER-dependent pathway. With high physiological concentration of estradiol or shutting down ERs by fulvestrant, it can disturb abnormal gastric cancer conditions caused by H. pylori infection. Our results may shed light on the intricate regulatory mechanism in human gastric cancer formation and progression.
Subjects
Gastric cancer
Helicobacter pylori
estradiol
estrogen receptors
cDNA microarray
regulatory mechanism
SDGs
Type
thesis
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