ECE2006 Poster Presentations Thyroid (174 abstracts)
Reverse Transcriptase (RT) inhibitors down regulate tumor growth, induce cell differentiation and re-establish iodine uptake in human thyroid anaplastic carcinoma in vitro and in vivo
M Landriscina 1 , A Fabiano 2 , S Altamura 1 , C Bagalà 3 , A Piscazzi 1 , N Maiorano 1 , F Giorgino 4 , C Barone 3 & M Cignarelli 1
1Clinical Oncology Unit, University of Foggia, Foggia, Italy; 2Endocrinology Unit, University of Foggia, Foggia, Italy; 3Clinical Oncology Unit, Catholic University, Rome, Italy; 4Endocrinology Unit, University of Bari, Bari, Italy.
RT-coding genes are expressed at very low levels in differentiated, non pathological tissues, while are significantly up-regulated in undifferentiated and transformed cells, suggesting a direct correlation between the level of expression of RT and the proliferative state of the cell. Either nevirapine and efavirenz, two RT inhibitors, used in the therapy of AIDS, reversibly down-regulate cell proliferation and induce differentiation in several human tumor cell lines.
We tested the pharmacological modulation of the endogenous RT activity as anticancer treatment in human thyroid anaplastic tumors. Efavirenz and nevirapine reversibly inhibited cell proliferation with no induction of apoptosis or necrosis in undifferentiated thyroid carcinoma ARO and FRO cells, two cell lines characterized by high levels of endogenous RT. This effect correlated with the accumulation of cells in G0/G1 phase of cell cycle, the appearance of morphological differentiation and a significant reprogramming of gene expression. Indeed, pharmacological inhibition of RT restored TSH signaling since induced the up-regulation of TSH receptor, thyroglobulin, TPO and pendrin genes, the TSH-dependent activation of NIS gene and re-established iodine uptake in response to TSH. Efavirenz reversibly down-regulated tumor growth in mice xenografts of ARO cells and restored iodine uptake in vivo, as well. Finally, nevirapine treatment up-regulated iodine uptake in a case of advanced undifferentiated thyroid tumor, insensitive to radiometabolic therapy. These findings suggest that endogenous RT inhibitors may represent a novel treatment in human undifferentiated thyroid tumors able to re-establish or improve the sensitivity to conventional radiometabolic therapy.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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