Type 2 iodothyronine deiodinase is highly expressed in medullary thyroid carcinoma

Meyer, Erika L. Souza; Goemann, Iuri Martin; Dora, José Miguel; Wagner, Marcius Comparsi; Maia, Ana Luiza

doi:10.1016/j.mce.2008.04.009

Cited by 18 publications

(9 citation statements)

References 51 publications

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“…In one study they observed poor correlation between the low D2 mRNA level and the enzymatic activity in papillary thyroid cancer but a statistically significant correlation between D2, Pax-8, and Titf1/Nkx-2 mRNA expression suggesting a potential role in the impairment of deiodinase expression (Ambroziak et al, 2005 ). D2 is also highly expressed in human medullary thyroid carcinoma (MTC), with activity that was comparable to those found in surrounding normal follicular tissue (Meyer et al, 2008 ).…”

Section: Type 2 Deiodinasementioning

confidence: 90%

Thyroid Hormone Deiodinases and Cancer

Casula¹,

Bianco²

2012

Front. Endocrin.

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Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation – in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches.

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Section: Type 2 Deiodinasementioning

confidence: 90%

Thyroid Hormone Deiodinases and Cancer

Casula¹,

Bianco²

2012

Front. Endocrin.

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“…D2 expression has rarely been associated with neoplastic transformation. It has been found upregulated in benign hyperfunctioning thyroid nodules and in thyroid tumors including follicular thyroid carcinoma, anaplastic and medullary thyroid cancer ( 54 , 55 ), whereas its expression was lower in papillary thyroid carcinoma than in normal thyroid tissues ( 56 ). This expression pattern is consistent with D2 being a cAMP-responsive gene whose expression increases in those tumoral contexts (thyroid adenoma and follicular carcinoma) in which there is a corresponding overstimulation of the cAMP pathway ( Table 1 ).…”

Section: D2 and Cancermentioning

confidence: 99%

Deiodinases and Cancer

et al. 2021

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Hormones are key drivers of cancer development, and alteration of the intratumoral concentration of thyroid hormone (TH) is a common feature of many human neoplasias. Besides the systemic control of TH levels, the expression and activity of deiodinases constitute a major mechanism for the cell-autonomous, pre-receptoral control of TH action. The action of deiodinases ensures tight control of TH availability at intracellular level in a time- and tissue-specific manner, and alterations in deiodinase expression are frequent in tumors. Research over the past decades has shown that in cancer cells, a complex and dynamic expression of deiodinases is orchestrated by a network of growth factors, oncogenic proteins and miRNA. It has become increasingly evident that this fine regulation exposes cancer cells to a dynamic concentration of TH that is functional to stimulate or inhibit various cellular functions. This review summarises recent advances in the identification of the complex interplay between deiodinases and cancer and how this family of enzymes is relevant in cancer progression. We also discuss whether deiodinase expression could represent a diagnostic tool with which to define tumor staging in cancer treatment or even a therapeutic tool against cancer.

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“…Activation of these signaling pathways produces cellular proliferation, which might favor cancer progression, and blockade of apoptotic processes and metastasis (Davis et al, 2016;Mousa et al, 2012Mousa et al, , 2018Weingarten et al, 2018). Moreover, separated evidences indicate that differences in deiodinase expression and differential splicing have been found in several cancers (Meyer et al, 2008) and increased TSHR expression have been detected in liver, ovarian, lung, and breast cancers (Table 1) (Govindaraj et al, 2012;Gyftaki et al, 2014;Kim et al, 2012;Shih et al, 2018;Tian et al, 2010). Moreover, it is known that TSHR is functional in the majority of human HCCs and that high TSHR expression is correlated with unfavorable postoperative outcome in patients with HCC receiving surgical treatment (Shih et al, 2018).…”

Section: Molecular Mechanisms Of Cancer In Thyroid Hormone Dysfunctionmentioning

confidence: 99%

Thyroid hormones in diabetes, cancer, and aging

et al. 2020

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Thyroid hormone (TH) production is a tightly regulated process controlled by a classic negative feedback loop involving the hypothalamus, the pituitary, and the thyroid, which has led to the common name hypothalamus-pituitary-thyroid axis (Figure 1). The thyrotropin-releasing hormone (TRH) is produced in the hypothalamus. Once released, TRH reaches the pituitary gland and binds to the TRH receptor and stimulates the production and secretion of thyroid-stimulating hormone (TSH), also known as thyrotropin (Liu et al., 2019). In the thyroid, TSH binds to the TSH receptor (TSHR) and induces TH production. When needed,

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Type 2 iodothyronine deiodinase is highly expressed in medullary thyroid carcinoma

Cited by 18 publications

References 51 publications

Thyroid Hormone Deiodinases and Cancer

Thyroid Hormone Deiodinases and Cancer

Deiodinases and Cancer

Thyroid hormones in diabetes, cancer, and aging

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