Increased Type 3 Deiodinase Expression in Papillary Thyroid Carcinoma

Romitti, Mírian; Wajner, Simone Magagnin; Zennig, Nadja; Goemann, Iuri Martin; Bueno, Ana Laura Andrade; Meyer, Erika L. Souza; Maia, Ana Luiza

doi:10.1089/thy.2012.0031

Cited by 36 publications

(45 citation statements)

References 37 publications

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“…As previously shown (Romitti et al 2012), DIO3 mRNA levels were significantly increased in PTC samples as compared with the levels observed in normal thyroid tissue (P!0.001). Samples harboring BRAF V600E mutation displayed higher levels of DIO3 expression as compared with those observed in samples with RET/PTC1 rearrangement or negative for BRAF V600E and RET/PTC1 alterations (7.97-vs 5.86-vs 5.85-fold respectively, P!0.001; Fig.…”

Section: Mapk Activation Induces Dio3 Levels In Ptc Cell Linessupporting

confidence: 72%

“…We have previously shown that MTC, a C-cell originated tumor, does not express D3 enzyme (Romitti et al 2012). Low levels of DIO3 mRNA were detected in MTC-derived TT cells while a marked increase in DIO3 expression was observed in recombinant SHH-treated TT cells (2.5-fold, P!0.001; Fig.…”

Section: Blockage Of Shh Pathway Prevents Dio3 Upregulation In Ptcmentioning

confidence: 76%

“…A potential role of D3 in tumorigenesis has been postulated due to DIO3 upregulation in several benign and malignant tumors (Pallud et al 1999, Huang et al 2005, Dentice et al . 2007, Romitti et al 2012. Studies performed in primary cultures of human fibroblasts showed that the DIO3 gene is induced by TGFB via SMAD and MAPK-dependent pathway (Huang et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The BRAF V600E mutation is the most common genetic event, observed in w50% of PTC, while RET/PTC rearrangement occurs in w20% and RAS mutations in 10-15% of cases (Kimura et al 2003, Fagin & Mitsiades 2008. Increased levels of D3 were shown in PTC and associated with advanced disease (Romitti et al 2012). Augmented D3 levels were also observed in follicular thyroid carcinoma but not in medullary or anaplastic thyroid carcinoma samples.…”

Section: Introductionmentioning

confidence: 97%

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MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Romitti¹,

Wajner²,

Ceolin³

et al. 2016

Endocrine-Related Cancer

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Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metast atic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples. DIO3 mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein. DIO3 gene silencing was performed via siRNA transfection. DIO3 mRNA levels and activity were readily detected in K1 (BRAF V600E ) and, at lower levels, in TPC-1 (RET/PTC1) cells (P!0.007 and PZ0.02 respectively). Similarly, DIO3 mRNA levels were higher in PTC samples harboring the BRAF V600E mutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P!0.001). Specific inhibition of BRAF oncogene (PLX4032, 3 mM), MEK (U0126, 10-20 mM) or p38 (SB203580, 10-20 mM) signaling was associated with decreases in DIO3 expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10 mM) resulted in markedly decreases in DIO3 mRNA levels. Interestingly, siRNA-mediated DIO3 silencing induced decreases on cyclin D1 expression and partial G1 phase cell cycle arrest, thereby downregulating cell proliferation. In conclusion, sustained activation of the MAPK and SHH pathways modulate the levels of DIO3 expression in PTC. Importantly, DIO3 silencing was associated with decreases in cell proliferation, thus suggesting a D3 role in tumor growth and aggressiveness.

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Section: Mapk Activation Induces Dio3 Levels In Ptc Cell Linessupporting

confidence: 72%

Section: Blockage Of Shh Pathway Prevents Dio3 Upregulation In Ptcmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Romitti¹,

Wajner²,

Ceolin³

et al. 2016

Endocrine-Related Cancer

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show abstract

“…In an opposite manner, miR21 positively regulates D3 expression in BCC through grainyhead-like 24:11 transcription factor 3 (GRHL3) (Di Girolamo et al 2016). The crosstalk between the SHH and MAPK pathways for D3 upregulation has also been demonstrated in human PTC cell lines (Romitti et al 2012(Romitti et al , 2016. Similarly, D3 depletion reduces cell proliferation and decreases cyclin D1 levels (Romitti et al 2016).…”

Section: Pi3k/protein Kinase B Pathwaymentioning

confidence: 80%

Role of thyroid hormones in the neoplastic process: an overview

Goemann¹,

Romitti²,

Meyer³

et al. 2017

Endocrine-Related Cancer

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Thyroid hormones (TH) are critical regulators of several physiological processes, which include development, differentiation and growth in virtually all tissues. In past decades, several studies have shown that changes in TH levels caused by thyroid dysfunction, disruption of deiodinases and/or thyroid hormone receptor (TR) expression in tumor cells, influence cell proliferation, differentiation, survival and invasion in a variety of neoplasms in a cell type-specific manner. The function of THs and TRs in neoplastic cell proliferation involves complex mechanisms that seem to be cell specific, exerting effects via genomic and nongenomic pathways, repressing or stimulating transcription factors, influencing angiogenesis and promoting invasiveness. Taken together, these observations indicate an important role of TH status in the pathogenesis and/or development of human neoplasia. Here, we aim to present an updated and comprehensive picture of the accumulated knowledge and the current understanding of the potential role of TH status on the different hallmarks of the neoplastic process.

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Thyroid Hormone, Cancer, and Apoptosis

Lin

Chin

Yang

et al. 2016

Comprehensive Physiology

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Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016.

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Increased Type 3 Deiodinase Expression in Papillary Thyroid Carcinoma

Cited by 36 publications

References 37 publications

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

Role of thyroid hormones in the neoplastic process: an overview

Thyroid Hormone, Cancer, and Apoptosis

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