Sonic hedgehog relates to colorectal carcinogenesis
Sonic hedgehog relates to colorectal carcinogenesis
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DOI：
10.1007/s00535-009-0110-2
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发表时间：
2009-08
影响因子：
6.3
通讯作者：
K. Yoshikawa;M. Shimada;Hidenori Miyamoto;Jun Higashijima;T. Miyatani;M. Nishioka;N. Kurita;T. Iwata;H. Uehara
中科院分区：
文献类型：
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作者：
K. Yoshikawa;M. Shimada;Hidenori Miyamoto;Jun Higashijima;T. Miyatani;M. Nishioka;N. Kurita;T. Iwata;H. Uehara
目的Hedgehog信号通路的激活是哺乳动物胃肠道正常发育的关键，与包括结直肠癌在内的多种肿瘤的发生发展密切相关。在胰腺中，与正常组织和癌症相比，前驱病变过度表达Sonic Hedgehog(Shh)。方法选择增生性息肉17例，结肠腺瘤24例，腺癌69例(高分化腺癌31例，中分化腺癌38例)和30例正常大肠组织作为研究对象。结果23例腺瘤中，22例(96%)表达Shh。在其他组中，17例增生性息肉中4例(24%)，31例高分化腺癌中7例(23%)，38例中分化腺癌中13例(34%)，30例正常组织中无一例表达Shh。结论Shh相关的癌变和Shh的表达可能是腺瘤-癌序列的触发因素。本研究提出了刺猬阻断致癌作用的潜在治疗靶点。
AimThe activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum.MethodsSeventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group.ResultsAlmost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression.ConclusionThis result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.