Activated β-catenin in the novel human parathyroid tumor cell line sHPT-1
2007 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 352, no 2, 532-536 p.Article in journal (Refereed) Published
Misregulation of the Wnt/beta-catenin signalling pathway is involved in the development and progression of many cancers. Recently, we presented evidence for aberrant accumulation of non-phosphorylated (stabilized) beta-catenin in benign parathyroid tumors from patients with primary hyperparathyroidism (pHPT) or HPT secondary to uremia (sHPT). Here we have used a human parathyroid hormone (PTH)-producing cell line (sHPT-1), established from a hyperplastic parathyroid gland removed at operation of a patient with sHPT, to further investigate the potential importance of beta-catenin in parathyroid tumorigenesis. Our studies demonstrate that efficient and specific knockdown of beta-catenin by small interfering RNA (siRNA) markedly decreased endogenous beta-catenin transcriptional activity as well as expression of the Wnt/beta-catenin target genes cyclin D1 and c-myc, known to be overexpressed in a substantial fraction of parathyroid tumors. Furthermore, siRNA to beta-catenin inhibited cellular growth and induced cell death. Growth and survival of the parathyroid tumor cells are thus dependent on maintained expression level of beta-catenin. The Wnt/beta-catenin signalling pathway, and beta-catenin in particular, presents a potential therapeutic target for HPT.
Place, publisher, year, edition, pages
2007. Vol. 352, no 2, 532-536 p.
β-Catenin, c-myc, Cyclin D1, Hyperparathyroidism, Parathyroid cell line, Wnt signalling
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-96472DOI: 10.1016/j.bbrc.2006.11.056ISI: 000243196300040PubMedID: 17126301OAI: oai:DiVA.org:uu-96472DiVA: diva2:171053