Activated β-catenin in the novel human parathyroid tumor cell line sHPT-1

Björklund, PeymanUppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery (författare)

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.

Åkerström, GöranUppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery(Swepub:uu)goranas (författare)
Westin, GunnarUppsala universitet,Institutionen för kirurgiska vetenskaper,Endokrinkirurgi, Endocrine Surgery(Swepub:uu)gunnwest (författare)
Uppsala universitetInstitutionen för kirurgiska vetenskaper (creator_code:org_t)

Ingår i:Biochemical and Biophysical Research Communications - BBRC: Elsevier BV352:2, s. 532-5360006-291X1090-2104

Av författaren/redakt...: Björklund, Peyma ...; Åkerström, Göran; Westin, Gunnar

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