Carcinogenic ability of Schistosoma haematobium possibly through oncogenic mutation of KRAS gene.

Mónica C Botelho, Isabel Veiga, Paula A Oliveira, Carlos Lopes, Manuel Teixeira, José M Correia da Costa, José C Machado
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Abstract

Schistosoma haematobium is a parasitic flatworm that infects millions of people, mostly in the developing world, and is associated with high incidence of bladder cancer, although why is not clear. Previously, we have used CD-1 mice to show that Schistosoma haematobium total antigen (Sh) has a carcinogenic ability. Sh intravesically instillation induced the development of several urothelial lesions, namely nodular hyperplasia and dysplasia (LGIUN-Low Grade Intra-Urothelial Neoplasia) after 40 weeks of treatment. These results suggested that Sh induce urothelium malignization. Bladder carcinoma frequently harbours gene mutations that constitutively activate the receptor tyrosine kinase-Ras pathway for this reason we studied activating mutations in KRAS gene. Twenty percent of the bladders with dysplasia presented a KRAS mutation in codon 12 of exon 2. We concluded from these results that the parasite extract of S. haematobium has carcinogenic ability possibly through oncogenic mutation of KRAS gene.

血血吸虫的致癌能力可能是通过KRAS基因的致癌突变。
血血吸虫是一种寄生扁虫,感染数百万人,主要是在发展中国家,它与膀胱癌的高发病率有关,尽管原因尚不清楚。在此之前,我们已经用CD-1小鼠证明了血血吸虫总抗原(Sh)具有致癌能力。经40周的治疗后,Sh静脉滴注诱导了几种尿路上皮病变的发展,即结节性增生和不典型增生(lgiun -低级别尿路上皮内瘤变)。提示Sh可诱导尿路上皮恶性化。膀胱癌经常含有组成性激活受体酪氨酸激酶- ras通路的基因突变,因此我们研究了KRAS基因的激活突变。20%的膀胱发育不良患者在2号外显子12密码子上出现KRAS突变。因此,我们认为血孢弧菌寄生提取物可能通过KRAS基因的致癌突变而具有致癌能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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