Am J Pathol  1999 Feb;154(2):325-9 

Frequent nuclear/cytoplasmic localization of beta-catenin without exon 3
mutations in malignant melanoma.

Rimm DL, Caca K, Hu G, Harrison FB, Fearon ER.

Department of Pathology, Yale University School of Medicine, New Haven,
Connecticut 06510, USA. david.rimm@yale.edu

Beta-Catenin has a critical role in E-cadherin-mediated cell-cell adhesion, and
it also functions as a downstream signaling molecule in the wnt pathway.
Mutations in the putative glycogen synthase kinase 3beta phosphorylation sites
near the beta-catenin amino terminus have been found in some cancers and cancer
cell lines. The mutations render beta-catenin resistant to regulation by a
complex containing the glycogen synthase kinase 3beta, adenomatous polyposis
coli, and axin proteins. As a result, beta-catenin accumulates in the cytosol
and nucleus and activates T-cell factor/ lymphoid enhancing factor transcription
factors. Previously, 6 of 27 melanoma cell lines were found to have beta-catenin
exon 3 mutations affecting the N-terminal phosphorylation sites (Rubinfeld B,
Robbins P, Elgamil M, Albert I, Porfiri E, Polakis P: Stabilization of
beta-catenin by genetic defects in melanoma cell lines. Science 1997,
275:1790-1792). To assess the role of beta-catenin defects in primary melanomas,
we undertook immunohistochemical and DNA sequencing studies in 65 melanoma
specimens. Nuclear and/or cytoplasmic localization of beta-catenin, a potential
indicator of wnt pathway activation, was seen focally within roughly one third
of the tumors, though a clonal somatic mutation in beta-catenin was found in
only one case (codon 45 Ser-->Pro). Our findings demonstrate that beta-catenin
mutations are rare in primary melanoma, in contrast to the situation in melanoma
cell lines. Nonetheless, activation of beta-catenin, as indicated by its nuclear
and/or cytoplasmic localization, appears to be frequent in melanoma, and in some
cases, it may reflect focal and transient activation of the wnt pathway within
the tumor.

PMID: 10027390 [PubMed - indexed for MEDLINE]