Concurrent expression of aryl hydrocarbon receptor and CYP1A1 but not CYP1A1 MspI polymorphism is correlated with gastric cancers raised in Dalian, China.
The frequency of cancer-associated m2m2- (C-) genotype of CYP1A1 and the factors contributing to the increased CYP1A1 expression in gastric cancers (GCs) are largely unknown. To address theses issues, PCR-restriction fragment length polymorphism (PCR-RFLP) was performed to elucidate the MspI polymorphism in 60 GC cases and 57 normal donor samples. The frequencies of m1m1-, m1m2- and m2m2-genotype were 43.3, 45 and 11.7% among GC patients and 45.6, 49.1 and 5.3% among the normal donors respectively, demonstrating no significant difference of them between cancer and control groups (chi(2)=0.343, P=0.558). The correlation of Aryl hydrocarbon receptor (AhR) with the frequent CYP1A1 expression in stepwise gastrocarcinogenesis was determined by RT-PCR, immunohistochemical staining (IHC) and Western blotting, using GC samples as well as their pre-malignant and non-cancerous counterparts. RT-PCR revealed that the AhR detection rates were 100, 94.12 and 85.17% in GC, pre-malignant and non-cancerous mucosa (P>0.05) respectively but the level of AhR expression in GCs was much higher than that of non-cancerous tissues. IHC showed that the frequencies of AhR detection were 94.87% (37/39) in GCs, 94.12% (16/17) in pre-malignant lesions and 50% (3/6) in non-cancerous mucosa, revealing significant difference in frequencies of AhR detection and levels of AhR expression between GC or pre-malignant group and non-cancerous one (P<0.05). The frequency of AhR nucleus translocation was significantly high in GCs (94.87%; 37/39) than that in pre-malignant (70.59%; 12/17) and especially in non-cancerous group (16.67%; 1/6). Co-existence of AhR nuclear translocation and CYP1A1 expressions were found in 82.70% (43/52) of GCs (r(s)=0.437, P<0.01). Our results suggest (1) that CYP1A1 MspI polymorphism may not contribute to the high gastric cancer risk in Dalian region and (2) that enhanced AhR expression and especially its nuclear translocation may be a favorable factor for GC formation presumably via up-regulating CYP1A1 expression.
Ma
Jing-Xin
JX
Cancer Institute and Liaoning Key Laboratory of Cancer Genimics, Dalian Medical University, 116027 Dalian, People's Republic of China.
Zhang
Kai-Li
KL
Liu
Xu
X
Ma
Yan-Lu
YL
Pei
Li-Na
LN
Zhu
Yi-Fang
YF
Zhou
Lei
L
Chen
Xiao-Yan
XY
Kong
Qing-You
QY
Li
Hong
H
Liu
Jia
J
D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D002681:China / Q000453:epidemiology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019003:Deoxyribonuclease HpaII / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D021381:Protein Transport; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic
D012334:RNA, Neoplasm; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019003:Deoxyribonuclease HpaII