Radioiodine therapy of thyroid carcinoma following Pax-8 gene transfer

Abstract

The thyroid transcription factor Pax-8 could bind with the promoter/enhancer of thyroid-specific genes such as thyroglobulin (Tg), thyroperoxidase (TPO) and sodium iodide symporter (NIS), and regulate the expression of these proteins in thyrocyte. Promoting iodide accumulation in tumor cells by re-expression of Pax-8 provides a possible strategy for radioiodine therapy of tumor. Therefore, we investigated the effect of Pax-8 gene transfer on radioiodine therapy of thyroid carcinoma. The human Pax-8 gene was transfected into the human thyroid carcinoma (K1 and F133) cells by the recombinant adenovirus vector. Although the NIS mRNA was not detected, the expression of mRNA and proteins of Tg and TPO in AdPax-8-infected F133 cells were activated by Pax-8. Iodide uptake in thyroid carcinoma cells was reactivated by Pax-8 (increasing 3.3-fold in K1 cells and 5.7-fold in F133 cells). Moreover, Pax-8 promoted iodide organification and the retention time of iodine in Pax-8-expressing cells apparently prolonged in vitro and in vivo (Po0.05). Pax-8-expressing thyroid carcinoma cells were selectively killed by radioiodine. The AdPax-8-infected tumors in vivo clearly visualized in scanning images at 12 h after administration of radioiodine. These results indicate that Pax-8 can promote iodide uptake, and specifically prolong the retention time of iodide in thyroid cancer in vitro and in vivo by promoting the expression of TPO and Tg proteins. Pax-8 gene transfection may lead to effective radioiodine therapy of tumor.

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFV600E by synergistically decreasing global trimethylation of H3K27

“…These phenomena have also been found in the study by Xing et al, indicating that other factors may be involved in the regulation of the expression of Tg and Tpo . Moreover, TPO was not obviously elevated in our study, which may compromise the final lethal effect of radioiodine on tumour cells, due to that iodide anion not organized by TPO undergoes rapidly efflux from cells, and a balance between NIS‐mediated iodide uptake and TPO‐mediated efflux determines the intracellular concentration and radiation dose of radioiodine …”

Hypothyroxinemia Induced by Mild Iodine Deficiency Deregulats Thyroid Proteins during Gestation and Lactation in Dams

“…It has been demonstrated that re-expression of PAX8 was associated with the recovery of the NIS mRNA expression in a rat thyroid cell line [42]. Furthermore, re-expression of PAX8 could promote iodine accumulation in human tumor cells [35,43]. The PAX8 and TTF1 are necessary to elevate levels of TSH [36].…”

Modulation of Sodium Iodide Symporter in Thyroid Cancer

“…For monolayer-cultured thyroid cells, and likely most thyroid cancer cells in patients, iodide organification may occur randomly at intracellular locations as the polarity of iodide influx and iodide efflux/organification may no longer exist. Pax-8 is the main transcription factor for Tg and TPO genes, and forced expression of Pax-8 by adenoviral vector in human anaplastic thyroid cancer cell lines, K-1 and F133, resulted in an increase in mRNA and protein levels of Tg and TPO, thereby resulting in an increase in iodide organification and retention [58]. Forced expression of both TTF-1 and Pax-8 further increased RAI uptake in K-1 and F133 cells by increasing NIS, Tg, and TPO expression levels [23].…”