The gene for the APC-binding protein beta-catenin (CTNNB1) maps to chromosome 3p22, a region frequently altered in human malignancies. Middleton SB, Frayling IM, Phillips RK. 2009 Jan;35(1):3-10. doi: 10.1016/j.ejso.2008.07.003. Eur J Surg Oncol. Increased beta-catenin may cause the growth advantage of cells in this tumor through a nuclear mechanism. APC contains seven 20 amino acid (20 aa) beta-catenin binding repeats that are required for beta-catenin turnover. Adenomatous polyposis coli (APC/Apc) gene encodes a key tumor suppressor whose mutations activate beta-catenin/T-cell factor (TCF)-mediated transcription (canonical Wnt signaling). Google Scholar. Sporadic aggressive fibromatosis (also called desmoid tumor) is a monoclonal proliferation of spindle (fibrocyte-like) cells that is locally invasive but does not metastasize. In some cases, this is caused by a somatic mutation resulting in a truncated APC protein.
M. Miyaki, M. Konishi, R. Kikuchi-Yanoshita, et al.Coexistence of somatic and germ-line mutations of APC gene in desmoid tumors from patients with familial adenomatous polyposis. APC helps regulate the cellular level of beta-catenin, which is a downstream mediator in Wnt (Wingless) signaling.
The increased protein level, relative to the RNA level, suggests that beta-catenin is degraded at a lower rate compared with normal tissues.
APC become mutated, beta-catenin is stabilized, accumulates in the cytoplasm, and gets in the nucleus, where it binds to lymphoid enhancer factor-T cell factor, and start new gene expression programs [14].
OpenUrl Abstract / FREE Full Text. Citation on PubMed. A similarity to abdominal fibromatoses (desmoids) in familial adenomatous polyposis and a cytogenetic study showing partial deletion of 5q in a subset of aggressive fibromatoses suggests that the adenomatous polyposis coli (APC) gene plays a role in its pathogenesis.
APC was a good substrate for GSK3 beta in vitro, and the phosphorylation sites were mapped to the central region of APC. It has been reported that genes and components of the Wnt signaling pathway are involved in brain neoplasms particularly those of epithelial origin [13].
Reverse transcription polymerase chain reaction showed that the tumors expressed N-cadherin but not E-cadherin (a pattern of expression of proteins making up adherens junctions similar to fibrocytes), suggesting that the specific adherens junctions present in epithelial cells are not necessary for beta-catenin function.
↵ Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P. Stabilization of beta-catenin by genetic defects in melanoma cell lines.
In addition to its well-established role in thymocyte development, recent studies have indicated that Wnt/β-catenin signaling is critical for the differentiation, polarization, and survival of mature T lymphocytes. APC contains seven 20 amino acid (20 aa) beta-catenin binding repeats that are required for beta-catenin turnover.
beta-Catenin has a nuclear function (binds transcription factors) and a cell membrane function (is a component of epithelial cell adherens junctions). 49.
Immunohistochemistry, using carboxy and amino terminus antibodies to APC, and DNA sequencing showed that three of the six contained an APC-truncating mutation, whereas normal tissues did not contain a mutation. Our biochemical studies show that phosphorylation of the APC 20 aa repeats increases the affinity of the repeats for beta-catenin by 300- to 500-fold and the phosphorylated 20 aa repeats prevent beta-catenin binding to Tcf. Cytogenet Cell Genet, 71 (4) (1995), pp.