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Endocrine Abstracts (2015) 37 GP30.04 | DOI: 10.1530/endoabs.37.GP.30.04

ECE2015 Guided Posters Endocrine tumours and neoplasia – General (7 abstracts)

Re-introduction of type 1 iodothyronine deiodinase in renal cancer cells affects their migration and expression of adhesion-related genes

Piotr Poplawski 1 , Joanna Boguslawska 1 , Hanna Kedzierska 1 , Beata Rybicka 1 , Zbigniew Tanski 2 , Theo J Visser 3 , Alicja Nauman 1, & Agnieszka Piekielko-Witkowska 1


1Department of Biochemistry and Molecular Biology, The Centre of Postgraduate Medical Education, Warsaw, Poland; 2Regional Hospital Ostroleka, Ostroleka, Poland; 3Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; 4Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland.


Introduction: Type 1 iodothyronine deiodinase (DIO1) is one of the three enzymes regulating bioavailability of thyroid hormones. In contrast to DIO2 and DIO3, the specific cellular role of DIO1 remains controversial. Our previous studies showed that DIO1 expression in clear cell renal cell carcinoma (ccRCC) is decreased, followed by lowered intracellular T3 concentration. In this study we explored how re-introduction of DIO1 in ccRCC cells affects their migration and proliferation.

Material: 75 matched pairs of ccRCC tumours and control samples, approved by the local Bioethical Committee. Two ccRCC cell lines KIJ-265T and KIJ-308T.

Methods: ccRCC cell lines (KIJ-265T-pcDNA3-DIO1 and KIJ-308T-pcDNA3-DIO1) with stable re-expression of DIO1 and control cell lines (KIJ-265T-pcDNA3 and KIJ-308T-pcDNA3) stably transfected with empty pcDNA3 vector were generated. The expression of genes involved in adhesion and ECM was analysed with RT2 Profiler PCR Array (SABiosciences), followed by SYBRGreen/qPCR validation. Scratch test and Cell Proliferation ELISA, BrdU were used for analysis of migration and proliferation respectively.

Results/conclusions: Expression of collagen COL1A1 and integrin ITGB2 was elevated in ccRCC tumours compared with control samples. Re-expression of DIO1 in KIJ-265T (grade IV) and KIJ-308T (grade II) cell lines resulted in decreased expression of COL1A1 (74 and 68% respectively) and ITGB2 (58 and 34% respectively). Scratch test revealed that migration of KIJ265 was stimulated by DIO1 expression while in KIJ308T DIO1 had no effect. Proliferation of both cells was reduced by DIO1 expression. We show, for the first time, that DIO1 has opposite roles in ccRCC tumourigenesis: it reduces proliferation with concomitant stimulation of migration in higher tumour grade cells. This effect is probably mediated by DIO1-induced changes in expression of genes involved in cellular adhesion. The specific mechanisms of DIO1 action in ccRCC require further investigation.

Disclosure: This work was supported by National Science Centre grants: 2012/05/B/NZ5/01541 (A Piekielko-Witkowska) and NN401611940 (A Nauman).

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