Ma Jing-Xin, Zhang Kai-Li, Liu Xu, Ma Yan-Lu, Pei Li-Na, Zhu Yi-Fang, Zhou Lei, Chen Xiao-Yan, Kong Qing-You, Li Hong, Liu Jia
Cancer Institute and Liaoning Key Laboratory of Cancer Genimics, Dalian Medical University, 116027 Dalian, People's Republic of China.
Cancer Lett. 2006 Aug 28;240(2):253-60. doi: 10.1016/j.canlet.2005.09.020. Epub 2005 Dec 6.
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.
细胞色素P450 1A1（CYP1A1）与癌症相关的m2m2-（C-）基因型的频率以及导致胃癌（GC）中CYP1A1表达增加的因素在很大程度上尚不清楚。为了解决这些问题，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对60例GC患者和57例正常供体样本进行MspI多态性分析。GC患者中m1m1-、m1m2-和m2m2-基因型的频率分别为43.3%、45%和11.7%，正常供体中分别为45.6%、49.1%和5.3%，表明癌症组与对照组之间无显著差异（χ2=0.343，P=0.558）。利用GC样本及其癌前和非癌对应样本，通过逆转录聚合酶链反应（RT-PCR）免疫组织化学染色（IHC）和蛋白质印迹法测定芳烃受体（AhR）与逐步胃癌发生过程中CYP1A1频繁表达的相关性。RT-PCR显示，GC、癌前和非癌黏膜中AhR的检出率分别为100%、94.12%和85.17%（P>0.05），但GC中AhR的表达水平远高于非癌组织。IHC显示，GC中AhR的检出频率为94.87%（37/39），癌前病变中为94.12%（16/17），非癌黏膜中为50%（3/6），表明GC或癌前组与非癌组之间AhR的检出频率和表达水平存在显著差异（P<0.05）。AhR核转位的频率在GC中（94.87%；37/39）显著高于癌前（70.59%；12/17），尤其是非癌组（16.67%；1/6）。在82.70%（43/52）的GC中发现AhR核转位与CYP1A1表达共存（rs=0.437，P<0.01）。我们的结果表明：（1）CYP1A1 MspI多态性可能与大连地区胃癌高风险无关；（2）AhR表达增强，尤其是其核转位可能是GC形成的有利因素，可能是通过上调CYP1A1表达实现的。
