日本京都大學(xué)的一個(gè)研究小組２日說(shuō),，幽門螺桿菌之所以能引發(fā)胃癌，是因?yàn)樗荛g接使抑制癌癥的基因變異失去效用,。
研究人員在《自然醫(yī)學(xué)》雜志網(wǎng)絡(luò)版上報(bào)告說(shuō),，他們?cè)谟^察感染幽門螺桿菌的胃粘膜時(shí)，意外發(fā)現(xiàn)其上皮細(xì)胞中承擔(dān)免疫功能的基因“ＡＩＤ”異?；钴S,。“ＡＩＤ”基因合成的“ＡＩＤ”酶能使“ｐ５３”等基因發(fā)生突變，導(dǎo)致后者失去抑制癌癥的效用,。研究人員用培養(yǎng)的人類胃部細(xì)胞進(jìn)行實(shí)驗(yàn)證實(shí),，正是幽門螺桿菌感染導(dǎo)致基因“ＡＩＤ”異常活躍,。
幽門螺桿菌是胃癌的罪魁禍?zhǔn)?，但幽門螺桿菌引發(fā)胃癌的具體機(jī)制此前一直沒(méi)有被發(fā)現(xiàn)。根據(jù)此次研究結(jié)果,，京都大學(xué)的研究人員認(rèn)為,，如果能開(kāi)發(fā)出以“ＡＩＤ”為目標(biāo)的基因療法，就有望防止胃癌發(fā)生,。
人是幽門螺桿菌的唯一自然宿主,。據(jù)估計(jì)，全世界約５０％的人胃部都“藏”有幽門螺桿菌,，但只有極少數(shù)人會(huì)受感染,，并因此患上胃炎、胃潰瘍或胃癌。
部分英文原文：
Nature Medicine,Published online: 1 April 2007; | doi:10.1038/nm1566
Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium
Yuko Matsumoto1, Hiroyuki Marusawa1, Kazuo Kinoshita2, Yoko Endo1, Tadayuki Kou1, Toshiyuki Morisawa1, Takeshi Azuma3, Il-Mi Okazaki4, Tasuku Honjo4 & Tsutomu Chiba1
1 Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
2 Evolutionary Medicine, Shiga Medical Center Research Institute, 5-4-30, Moriyama, Shiga 524-8524, Japan.
3 Frontier Medical Science in Gastroenterology, International Center for Medical Research and Treatment, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
4 Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Correspondence should be addressed to Tsutomu Chiba [email protected]
Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IB kinase–dependent nuclear factor-B activation pathway. H. pylori–mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori–associated gastric carcinogenesis.
