Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon.

Anderson CB; Neufeld KL; White RL

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Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon.

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Mutations in the APC tumor suppressor gene are present in approximately 85 of colorectal tumors and are thought to contribute early in the process of tumorigenesis. The truncated protein resulting from most APC mutations can lead to elevated beta-catenin levels in colon tumor cells. APC and associated proteins thus form a beta-catenin regulatory complex, with axin playing a key role. Although cell culture studies have revealed intriguing aspects of this complex, little characterization has been done in human colonocytes, the target tissue of colon carcinogenesis. The present study of intact human colon crypts, adenomatous polyps, and adenocarcinomas focuses on subcellular localization of some key elements of the complex: beta-catenin, APC, axin, and axin2. We examined endogenous protein localization within the framework of three-dimensional tissue architecture by using laser scanning confocal microscopy, and immunofluorescence staining of whole-mount fixed tissue from more than 50 patients. Expression patterns suggest that APC and axin colocalize in the nucleus and at lateral cell borders, and show that axin2 is limited to the nucleus. Altered nuclear expression of axin seen in colon polyps and carcinomas may be a consequence of the loss of full-length APC and the advent of nuclear beta-catenin. The observation of nuclear beta-catenin in fewer than half of carcinoma images and only rarely in polyps indicates that nuclear translocation of beta-catenin may not be an immediate consequence of the loss of APC.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2002年第13期|8683-8688|共6页
作者
Anderson CB; Neufeld KL; White RL;
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作者单位

Eccles Institute of Human Genetics and Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA. chris.anderson;

hysiol.ox.ac.uk;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Colon; Colorectal Neoplasms; Proto-Oncogene Proteins; Subcellular Fractions; 结肠; 结肠直肠肿瘤; 原癌基因蛋白质类; 亚细胞部分;

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Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon.

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