%0 Journal Article
%T Stabilizing mutation of CTNNB1/beta-catenin and protein accumulation analyzed in a large series of parathyroid tumors of Swedish patients
%A Peyman Bj£¿rklund
%A Daniel Lindberg
%A G£¿ran £¿kerstr£¿m
%A Gunnar Westin
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-53
%X The mutation S37A (TCT > GCT) was detected by direct DNA sequencing of PCR fragments in 6 out of 104 sporadic parathyroid adenomas (5.8%). Taking our previous study into account, a total of 9 out of 124 (7.3%) adenomas displayed the same mutation. The mutations were homozygous by DNA sequencing, restriction enzyme cleavage, and gene copy number determination using the GeneChip 500 K Mapping Array Set. All tumors analyzed by immunohistochemistry, including those with mutation, displayed aberrant ¦Â-catenin accumulation. Western blotting revealed a slightly higher expression level of ¦Â-catenin and nonphosphorylated active ¦Â-catenin in tumors with mutation compared to those without. Presence of the mutation was not related to distinct clinical characteristics.Aberrant accumulation of ¦Â-catenin is very common in parathyroid tumors, and is caused by stabilizing homozygous mutation in 7.3% of Swedish pHPT patients.Parathyroid disease with hypersecretion of parathyroid hormone and generally also hypercalcemia occurs in primary hyperparathyroidism (pHPT), due to growth regulatory disturbance in one or several parathyroid glands. Activation of CCND1 oncogene expression or inactivation of the MEN1 tumor suppressor gene contributes to deregulated growth control in a fraction of sporadic parathyroid adenomas [1-4].Activation of the Wnt/¦Â-catenin signaling pathway by aberrant accumulation of stabilized ¦Â-catenin is involved in the development of many neoplasms. ¦Â-catenin accumulation is typically caused by mutations in components of the signaling pathway, such as APC, Axin, ¦Â-Trcp, and WTX, or results from secondary events. In addition, protein stabilizing mutations in the glycogen synthase kinase 3¦Â phosphorylation sites of ¦Â-catenin (Ser-33, Ser-37, Thr-41, Ser-45) occur with varying frequency in several neoplasms [5-9].We recently reported activation of the Wnt/¦Â-catenin signaling pathway by aberrant accumulation of ¦Â-catenin in parathyroid adenomas from patients with pHPT [10
%U http://www.molecular-cancer.com/content/7/1/53