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PMID: 17572842 Published · ppublish English Journal Article Review

Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia.

Medical molecular morphology ·Vol. 40 ·No. 2 ·2007-06-00 ·Pages 68-81

Senda T, Iizuka-Kogo A, Onouchi T, Shimomura A

Abstract

The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in most sporadic colorectal tumors. During both embryonic and postnatal periods, APC is widely expressed in a variety of tissues, including the brain and gastrointestinal tract. The APC gene product (APC) is a large multidomain protein consisting of 2843 amino acids. APC downregulates the Wnt signaling pathway through its binding to beta-catenin and Axin. Most mutated APC proteins in colorectal tumors lack the beta-catenin-binding regions and fail to inhibit Wnt signaling, leading to the overproliferation of tumor cells. Several mouse models (APC580D, APCDelta716, APC1309, APCMin, APC1638T) have been established to investigate carcinogenesis caused by APC mutations. APC also binds to APC-stimulated guanine nucleotide exchange factor, the kinesin superfamily-associated protein 3, IQGAP1, microtubules, EB1, and discs large (DLG). APC has both nuclear localization signals and nuclear export signals in its molecule, suggesting its occasional nuclear localization and export of beta-catenin from the nucleus. APC is highly expressed in the intestinal and colorectal epithelia and may be involved in homeostasis of the enterocyte renewal phenomena, in which proliferation, migration, differentiation, and apoptosis are highly regulated both temporally and spatially. Through the many binding proteins mentioned, APC can exert multiple functions involved in epithelial homeostasis.

MeSH Terms
Adenomatous Polyposis Coli Protein/deficiency,metabolism Animals Binding Sites/genetics Colon/physiology,physiopathology Colorectal Neoplasms/metabolism,physiopathology Epithelium/physiology,physiopathology Gene Expression Regulation, Neoplastic Genes, APC Humans Mice Mice, Knockout Microtubules/metabolism Mutation/genetics Protein Binding/genetics Rats Repressor Proteins/metabolism Signal Transduction
Chemicals
Adenomatous Polyposis Coli Protein Repressor Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Senda Takao
Department of Anatomy I, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan. tsenda@fujita-hu.ac.jp
Iizuka-Kogo Akiko
Onouchi Takanori
Shimomura Atsushi
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Article Info
Journal
Medical molecular morphology
Abbr.
Med Mol Morphol
ISSN
1860-1480
DOI
10.1007/s00795-006-0352-5
Email
tsenda@fujita-hu.ac.jp
Published
2007-06-00
Epub
2007-00-18
Pages
68-81
Language
English
Region
Japan
NLM ID
101239023
Subset
IM
External Links
PubMed source DOI: 10.1007/s00795-006-0352-5 View journal details
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