INCREASED TYPE 3 DEIODINASE EXPRESSION IN PAPILLARY THYROID CARCINOMA.
Summary of "INCREASED TYPE 3 DEIODINASE EXPRESSION IN PAPILLARY THYROID CARCINOMA."
Background: Thyroid hormone regulates a wide range of cellular activities, including the balance between cell proliferation and differentiation. The thyroid hormone-inactivating type 3 deiodinase (DIO3, D3) has been shown to be reactivated in human neoplasias. Here, we evaluated DIO3 expression in human papillary thyroid carcinoma (PTC). Methods: DIO3 mRNA levels were measured by Real-Time PCR and D3 activity by paper-descendent chromatography. BRAFV600E mutation was identified in DNA from paraffin-embedded tissues by direct sequencing. Results: Increased D3 activity was detected in all twenty-six PTC samples analyzed. The augment in D3 activity were paralleled by increased levels of DIO3 mRNA (~5 fold). DIO3 transcripts in K1 PTC-derived cell line were further up-regulated by the transforming growth factor β (TGFβ) while markedly induction of DIO3 occurred when BRAFV600E mutation was present, suggesting that D3-induction might to be mediated through the mitogen-activated protein kinase (MAPK) signaling pathway, which is constitutively activated in this tumor. Remarkable, DIO3 mRNA and activity were significantly higher in BRAFV600E mutated samples (P=0.001). Increased D3 activity was correlated with tumor size (r=0.68, P=0.003), and associated with lymph node (P=0.03) or distant metastasis (P=0.006) at diagnosis. Interestingly, decreased levels of type 2 deiodinase (DIO2) gene were observed in PTC but not in follicular lesions. DIO2 down-regulation might contribute to further decreases in intracellular thyroid hormone levels. Conclusions: Taken together, these findings indicate that intracellular hypothyroidism might be associated with the degree of cell proliferation and enhancement of tumor invasiveness in human PTC.
Affiliation
Hospital de Clínicas de Porto Alegre, Internal Medicine / Endocrinology, Rua Ramiro Barcelos 2350, Porto Alegre, RS, Brazil, 90035-003, 55-51-21018127, 55-51-21018777; almaia@ufrgs.br.
Journal Details
This article was published in the following journal.
Name: Thyroid : official journal of the American Thyroid Association
ISSN: 1557-9077
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22551618
- DOI: http://dx.doi.org/10.1089/thy.2012-0031
Medical and Biotech [MESH] Definitions
Carcinoma, Papillary, Follicular
A thyroid neoplasm of mixed papillary and follicular arrangement. Its biological behavior and prognosis is the same as that of a papillary adenocarcinoma of the thyroid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1271)
Carcinoma, Renal Cell
A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.
Carcinoma, Medullary
A carcinoma composed mainly of epithelial elements with little or no stroma. Medullary carcinomas of the breast constitute 5%-7% of all mammary carcinomas; medullary carcinomas of the thyroid comprise 3%-10% of all thyroid malignancies. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1141; Segen, Dictionary of Modern Medicine, 1992)
Multiple Endocrine Neoplasia Type 2b
Similar to MEN2A, it is also caused by mutations of the MEN2 gene, also known as the RET proto-oncogene. Its clinical symptoms include medullary carcinoma (CARCINOMA, MEDULLARY) of THYROID GLAND and PHEOCHROMOCYTOMA of ADRENAL MEDULLA (50%). Unlike MEN2a, MEN2b does not involve PARATHYROID NEOPLASMS. It can be distinguished from MEN2A by its neural abnormalities such as mucosal NEUROMAS on EYELIDS; LIP; and TONGUE, and ganglioneuromatosis of GASTROINTESTINAL TRACT leading to MEGACOLON. It is an autosomal dominant inherited disease.
Multiple Endocrine Neoplasia Type 2a
A form of multiple endocrine neoplasia characterized by the presence of medullary carcinoma (CARCINOMA, MEDULLARY) of the THYROID GLAND, and usually with the co-occurrence of PHEOCHROMOCYTOMA, producing CALCITONIN and ADRENALINE, respectively. Less frequently, it can occur with hyperplasia or adenoma of the PARATHYROID GLANDS. This disease is due to gain-of-function mutations of the MEN2 gene on CHROMOSOME 10 (Locus: 10q11.2), also known as the RET proto-oncogene that encodes a RECEPTOR PROTEIN-TYROSINE KINASE. It is an autosomal dominant inherited disease.
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