Enzymatic activity of type 1 iodothyronine deiodinase in selected liver tumors

Abstract

IntroductionType 1 iodothyronine deiodinase (D1) converts thyroxin (T4) into tri-iodothyronine (T3). Strong evidence indicates that thyroid hormone metabolism is disturbed in neoplasms such as thyroid and breast cancer. However, there is limited data concerning the function of the D1 enzyme in liver tumors. We aimed to estimate the enzymatic activity of D1 in two different common liver tumors.Material and methodsWe obtained 20 tumor samples from patients who had undergone a liver resection. Of the tissue samples, there were 13 benign lesions of focal nodular hyperplasia (FNH) and 7 malignant lesions of hepatocellular carcinomas (HCC). The D1 activity was assessed by measuring the amount of radioactive iodine released in reaction to D1-catalysed deiodination. Groups were compared by the Mann-Whitney non-parametrical test for independent trials, and the Kruskal Wallis test.ResultsThe enzymatic activity of D1 was not significantly altered in the FNH group (median = 536 fmol/mg of protein/min; p = 0.972) and HCC group (367 fmol/mg; p = 0.128) when compared to matched normal liver parenchyma controls (546 fmol/mg and 556 fmol/mg, respectively).ConclusionsLiver parenchyma expresses high levels of D1. The results clearly revealed that D1 activity was not significantly different between benign and malignant tumors (FNH and HCC) compared to healthy liver parenchyma cells.

Prognostic significance of cyclooxygenase-2 expression in patients with hepatocellular carcinoma: a meta-analysis

“…Second, the OS and DFS outcomes were based on individual unadjusted RRs. Thus, a more precise assessment should be adjusted using other prognostic factors [ 32 ]. Third, no clear guidelines are available as regards the methods used for the evaluation of the levels of COX-2 in HCC patients.…”

Current concepts and challenges to unravel the role of iodothyronine deiodinases in human neoplasias

“…In an analysis of 13 benign lesions and 7 samples of hepatocellular carcinoma that were compared to normal tissue, there was no difference in DIO1 activity (Kornasiewicz et al 2014); however, DIO1 activity was decreased in hepatic hemangiomas (Kornasiewicz et al 2010). HepG2 express functional DIO1 (van Stralen et al 1996, Chen et al 2016 but neither DIO2 or DIO3 activity has been observed in these cells (Kester et al 2006).…”

Role of thyroid hormones in the neoplastic process: an overview

“…In renal clear cell cancer, miR-224 expression correlates negatively with the DIO1 mRNA level and T 3 concentration, suggesting that miR-224 induces intracellular hypothyroidism via reduced D1 function (Boguslawska et al 2011). Interestingly, D1 activity does not differ significantly between benign and malignant tumors as compared with healthy liver parenchyma cells (Kornasiewicz et al 2014). In contrast, D1 activity in non-cancerous breast tissues is very low or non-measurable, whereas it is increased in breast cancer, indicating a tissue-specific regulation of D1 expression (Debski et al 2007).…”