Abstracts - Orals, Featured Poster Presentations, and Posters
SUN 303-321-Cancer in Endocrine Tissues
Bench to Bedside
Expo Halls ABC (Moscone Center)
Poster Board SUN-305
Aberrant expression and mutations of thyroid hormone receptor genes (TRs) are closely associated with some human cancers. Indeed, TRbeta knock-out or the expression of a mutant form unable to bind the hormone may be related to follicular thyroid carcinoma development in mice. This event involves a modulatory signal to pathways regulating cell growth and survival, cell invasion and angiogenesis. On the other hand, it has been reported that other mechanisms (e.g. impaired thyroid homeostasis) may lead to cancer development, perhaps by modulating thyroid receptors status and expression. Peculiar action of hormone/thyroid receptors interaction may thus influence thyroid carcinoma progression and differentiation. In this study, we evaluated the influence of T3 on the tumorigenicity in two different thyroid carcinoma cell lines expressing high levels of thyroid receptors. Human papillary thyroid carcinoma (PTC) cells and human anaplastic thyroid carcinoma (FRO) cells have been used and tested for their responsivity to T3 treatment. Exposure to 100 nM of T3 was able to inhibit cell proliferation in both systems; depletion of proliferating cells up to 25-30%, was demonstrated by cell growth analysis and MTT assay. Then, tumor progression and invasiveness have been analyzed. The clonogenicity assay revealed that T3 treatment inhibits new clones formation by 30% in the FRO cells and by 20% in the PTC. Furthermore, T3 exposure inhibited the invasiveness of both cells by 50% in the FRO cells and 65% in the PTC, as demonstrated by matrigel assay. In keeping with these results, the activation and expression levels of some main molecules such as PTEN, p53, MDM2, CXCR4 underlying these specific tumorigenic properties , together with some key regulator of cell proliferation and survival, namely ccnD1, ccnA1, ccnE, cdk6,cdk 4 and Bax had been analyzed by RT-PCR.
In conclusion, these data demonstrated that T3 treatment, when in the presence of high thyroid receptor expression, may play an inhibitory role on growth and tumorigenic properties of differentiated and undifferentiated thyroid carcinoma cells.
Nothing to Disclose: CV, AF, FA, MGS, CV, SM, MC
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