title: Induction of type 1 iodothyronine deiodinase expression inhibits proliferation and migration of renal cancer cells.
abstract: Type 1 iodothyronine deiodinase (DIO1) regulates peripheral metabolism of thyroid hormones that control cellular proliferation, differentiation and metabolism. The significance of DIO1 in cancer is unknown. In this study we hypothesized that diminished expression of DIO1, observed in renal cancer, contributes to the carcinogenic process in the kidney. Here, we demonstrate that ectopic expression of DIO1 in renal cancer cells changes the expression of genes controlling cell cycle, including cyclin E1 and E2F5, and results in inhibition of proliferation. The expression of genes encoding collagens (COL1A1, COL4A2, COL5A1), integrins (ITGA4, ITGA5, ITGB3) and transforming growth factor-β-induced (TGFBI) is significantly altered in renal cancer cells with induced expression of DIO1. Finally, we show that overexpression of DIO1 inhibits migration of renal cancer cells. In conclusion, we demonstrate for the first time that loss of DIO1 contributes to renal carcinogenesis and that its induced expression protects cells against cancerous proliferation and migration.
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Poplawski
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Rybicka
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Boguslawska
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Rodzik
authors.affiliation: Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813, Warsaw, Poland; Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, 02-089, Warsaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Nauman
authors.affiliation: Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813, Warsaw, Poland. Electronic address: apiekielko@cmkp.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Piekielko-Witkowska
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D050700:E2F5 Transcription Factor / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism; D015291:Transforming Growth Factors / Q000378:metabolism
chemical_list: D019927:Cyclin E; D050700:E2F5 Transcription Factor; D013963:Thyroid Hormones; D015291:Transforming Growth Factors; D003094:Collagen; D007453:Iodide Peroxidase
keywords: Adhesion; Migration; Proliferation; Renal cancer; Type 1 iodothyronine deiodinase