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

Misregulation of the Wnt/β-catenin signalling pathway is involved in the development and progression of many cancers. Recently, we presented evidence for aberrant accumulation of non-phosphorylated (stabilized) β-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 β-catenin in parathyroid tumorigenesis. Our studies demonstrate that efficient and specific knockdown of β-catenin by small interfering RNA (siRNA) markedly decreased endogenous β-catenin transcriptional activity as well as expression of the Wnt/β-catenin target genes cyclin D1 and c-myc, known to be overexpressed in a substantial fraction of parathyroid tumors. Furthermore, siRNA to β-catenin inhibited cellular growth and induced cell death. Growth and survival of the parathyroid tumor cells are thus dependent on maintained expression level of β-catenin. The Wnt/β-catenin signalling pathway, and β-catenin in particular, presents a potential therapeutic target for HPT.