Carcinogenesis of intestinal-type gastric cancer and colorectal cancer is commonly accompanied by expression of brain (fetal)-type glycogen phosphorylase.

Carcinogenesis of intestinal-type gastric cancer and colorectal cancer is commonly accompanied by expression of brain (fetal)-type glycogen phosphorylase.
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肠型胃癌和结直肠癌的癌变通常伴随着脑(胎儿)型糖原磷酸化酶的表达。

DOI:
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发表时间:
1999
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
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通讯作者:
M. Ogawa
M. Ogawa
中科院分区:
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文献类型:
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作者:
Shinya Shimada;S. Tashima;Kenji Yamaguchi;H. Matsuzaki;M. Ogawa

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我们以前的研究表明,糖原磷酸化酶(GP)在胃癌和肠上皮化生(IM)的增殖细胞中具有显著的酶活性。本文就GP在胃肠道肿瘤中的亚型鉴定及其在胃肠道肿瘤发生中作用的研究进展作一综述。聚合酶链反应(PCR)分析显示,在胃癌中表达的唯一亚型是脑型GP(BGP)。本文对136例胃癌、96例结直肠手术切除标本和55例内镜切除的结直肠腺瘤标本中BGP、癌基因产物和增殖细胞核抗原在胃癌、结直肠癌及其癌前病变和正常粘膜中的表达进行了检测。免疫组化显示BGP通常存在于胃肠道型胃癌(80.6%)和结直肠癌(83.3%)中,而在正常人胃和大肠粘膜中未观察到BGP表达,除了下面描述的BGP病灶。BGP阳性的IM与胃癌的发生密切相关,部分IM同时表达p53蛋白。BGP在“腺瘤癌序列”(ACS)中的表达与异型增生的增加有很好的相关性,并先于p53表达。PCR-单链构象多态性分析显示,BGP灶中p53基因突变频率较高(41.2%)。提示BGP是一种新的胃癌发生的生物标志物,可作为ACS和原发性结直肠癌发生的生物标志物。
Our previous studies have demonstrated the significant enzymatic activity of glycogen phosphorylase (GP) in the gastric carcinoma and proliferating cells of particular intestinal metaplasia (IM). This paper reviewed the identification of the GP isoform in the gastrointestinal carcinoma, and the investigation on the role of this molecule in the gastrointestinal carcinogenesis. The only isoform expressed in gastric cancer was brain-type GP (BGP) using polymerase chain reaction (PCR) analysis. The expression of BGP, oncogene products and proliferating cell nuclear antigen in the gastric and colorectal carcinomas, their premalignant lesions, and the normal mucosa were examined using 136 gastric and 96 colorectal surgically resected specimens, and 55 endoscopically resected colorectal adenomas. The BGP visualized by immunohistochemistry was commonly present in intestinal-type gastric (80.6%) and colorectal (83.3%) carcinomas, whereas no BGP expression was seen in the normal human gastric and large intestinal mucosa except in the BGP foci described below. IMs with BGP had close correlation with intestinal-type gastric carcinoma, and some of them coexpressed accumulated p53 protein. The expression of BGP during 'adenoma carcinoma sequence' (ACS) showed excellent correlation with the increased dysplasia and was found prior to p53 expression. Positive staining in overtly normal looking colonic mucosa (BGP foci) was observed mainly around carcinomas without any adenoma component, and frequent p53 mutation (41.2%) was detected in the BGP foci using PCR-single strand conformation polymorphism analysis. It is suggested that BGP is a novel biomarker for carcinogenesis in the intestinal-type gastric carcinoma and in both of the pathways of ACS and the 'de novo' colorectal carcinoma.