Proto-oncogene PBF/PTTG1IP regulates thyroid cell growth and represses radioiodide treatment

Pituitary tumor transforming gene (PTTG)-binding factor (PBF or PTTG1IP) is a little characterized protooncogene that has been implicated in the etiology of breast and thyroid tumors. In this study, we created a murine transgenic model to target PBF expression to the thyroid gland (PBF-Tg mice) and found that these mice exhibited normal thyroid function, but a striking enlargement of the thyroid gland associated with hyperplastic and macrofollicular lesions. Expression of the sodium iodide symporter (NIS), a gene essential to the radioiodine ablation of thyroid hyperplasia, neoplasia, and metastasis, was also potently inhibited in PBF-Tg mice. Critically, iodide uptake was repressed in primary thyroid cultures from PBF-Tg mice, which could be rescued by PBF depletion. PBF-Tg thyroids exhibited upregulation of Akt and the TSH receptor (TSHR), each known regulators of thyrocyte proliferation, along with upregulation of the downstream proliferative marker cyclin D1. We extended and confirmed findings from the mouse model by examining PBF expression in human multinodular goiters (MNG), a hyperproliferative thyroid disorder, where PBF and TSHR was strongly upregulated relative to normal thyroid tissue. Furthermore, we showed that depleting PBF in human primary thyrocytes was sufficient to increase radioiodine uptake. Together, our findings indicate that overexpression of PBF causes thyroid cell proliferation, macrofollicular lesions, and hyperplasia, as well as repression of the critical therapeutic route for radioiodide uptake

Thyroglobulin-the prothyroid hormone : progress in endocrine research and therapy

xvii, 341 p.; 24 cm

Dexamethasone inhibits tumor necrosis factor-α-induced apoptosis and interleukin-1β release in human subcutaneous adipocytes and preadipocytes1

Tumor necrosis factor-α (TNFα) can decrease adipose tissue mass, but in obesity, adipose tissue hypertrophy persists despite increased TNFα expression. The hormonal milieu of obesity may antagonize the adipostat effects of TNFα. We examined the effects of insulin and the synthetic glucocorticoid, dexamethasone (Dex), on TNFα-induced apoptosis and gene expression in human adipocytes and preadipocytes. Using RT multiplex PCR, the expression of the proapoptotic genes interleukin-1β (IL-1β)-converting enzyme (ICE) and TNFα and the antiapoptotic genes bcl-2, nuclear factor-κB (NFκB), and NFκB inhibitory subunit, IκB, were examined. The expression and release of IL-1β, a postulated downstream effector of ICE-mediated apoptosis, were also determined. TNFα increased the messenger ribonucleic acid levels of ICE, TNFα, IL-1β, bcl-2, and NFκB in preadipocytes and adipocytes (P < 0.01). Dex inhibited TNFα-induced messenger ribonucleic acid expression of ICE, TNFα, and IL-1β (P < 0.01), but not that of bcl-2 and NFκB. TNFα stimulated IL-1β release from preadipocytes and adipocytes up to 20-fold, but the effect was abrogated by Dex. Apoptosis induced by TNFα was reduced to control levels (P < 0.01) by Dex. Insulin had no significant effect on TNFα-induced apoptosis and gene expression. In obesity, glucocorticoids may reduce TNFα actions in adipose tissue by inhibiting TNFα-induced apoptosis, IL-1β release, and TNFα expression

A new approach to the isolation of TSH receptor proteins

info:eu-repo/semantics/publishe