Analysis of the mitochondrial D-loop sequence in a patient with thyroid Hurthle cell carcinoma and sacral bone metastasis / 대한내과학회지

Hurthle cell carcinoma, an oncocytic variant of follicular thyroid carcinoma, has a higher malignancy potential than well differentiated thyroid carcinomas. It has a tendency to metastasize easily to the lungs and bones, although isolated sacral bone metastasis has been rarely reported. Hurthle cell carcinoma has been characterized by increased mitotic activity and abundant abnormal mitochondria, which have profound mitochondrial DNA (mtDNA) alterations. In general, a well-known hypothesis is that genomic alteration, especially microsatellite instability of the mtDNA D-loop, might result in whole mtDNA instability as seen in Hurthle cell carcinoma. Recently, we experienced a case of Hurthle cell carcinoma that presented with extensive sacral bone metastasis. To investigate the relationship between mtDNA genomic instability and metastatic potential in this case, we performed direct sequencing of the mtDNA D-loop in samples extracted from normal thyroid tissue, thyroid carcinoma tissue, and sacral bone metastasis tissue. Here, we describe the results of mtDNA D-loop sequencing and present a literature review.

Regulation of Inhibitors of Differentiation Family Proteins by Thyroid-Stimulating Hormone in FRTL-5 Thyroid Cells

Members of the inhibitors of differentiation (Id) family of helix-loop-helix (HLH) proteins are known to play important roles in the proliferation and differentiation of many cell types. Thyroid-stimulating hormone (TSH) regulates proliferation and differentiation by activating TSH receptor (TSHR) in thyrocytes. In this study, we found that Id2, one of the Id family proteins, is a major target for regulation by TSH in FRTL-5 thyroid cells. TSH rapidly increases the Id2 mRNA level in FRTL-5 thyroid cells but the Id2 protein showed biphasic regulatory patterns, being transiently reduced and subsequently induced by TSH treatment. Transient reduction of Id2 protein was noted within 2 hr of TSH treatment and was mediated by proteasomal degradation. Moreover, reduced Id2 expression correlated with the activity of the phosphatidylinositol 3 kinase pathway, which is activated by TSH. Although TSH increases the activity of the Id2 promoter, TSH-induced activation of this promoter was independent of c-Myc. Id2 did not alter TTF-1- and Pax-8-mediated effects on the regulation of the Tg promoter. Thus, in summary, we found that TSH regulates Id2 expression, but that Id2 does not alter the expression of thyroid-specific genes, such as Tg, in FRTL-5 thyroid cells.