Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer.
OBJECTIVE
To determine the functional significance of aryl hydrocarbon receptor (AhR) in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer (GC) treatment.


METHODS
RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.


RESULTS
AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase.


CONCLUSIONS
AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.
Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou, Guangdong Province, China.
Tie-Li
TL
Peng
Jie
J
Chen
Wei
W
Mao
Xin
X
Liu
Yu
Y
Tao
Lian-Zhou
LZ
Chen
Min-Hu
MH
Chen
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004785:Environmental Pollutants / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013270:Stomach / Q000166:cytology / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon