Thyroid hormone - triiodothyronine - has contrary effect on proliferation of human proximal tubules cell line (HK2) and renal cancer cell lines (Caki-2, Caki-1) - role of E2F4, E2F5 and p107, p130

Piotr Poplawski,Alicja Nauman

doi:10.1186/1756-6614-1-5

Abstract

BackgroundTriiodothyronine regulates proliferation acting as stimulator or inhibitor. E2F4 and E2F5 in complexes with pocket proteins p107 or p130 stop cells in G1, repressing transcription of genes important for cell cycle progression. p107 and p130 inhibits activity of cyclin/cdk2 complexes. Expression of all those proteins could be regulated by triiodothyronine. In clear cell renal cell carcinoma many disturbances in T3 signaling pathway was described, in that type of cancer also expression of some key G1 to S phase progression regulators was shown.MethodsWe investigated role of T3 and its receptors in regulation of proliferation of HK2, Caki-2, Caki-1 cell lines (cell counting, cytometric analysis of DNA content) and expression of thyroid hormone receptors, E2F4, E2F5, p107 and p130 (western blot and semi-quantitative real time PCR). Statistical analysis was performed using one-way ANOVA.Results and ConclusionWe show that T3 inhibits proliferation of HK2, and stimulates it in Caki lines. Those differences are result of disturbed expression of TR causing improper regulation of E2F4, E2F5, p107 and p130 in cancer cells.

Highlights

Triiodothyronine regulates proliferation acting as stimulator or inhibitor
Western blot and flow cytometry cells were harvested by trypsynization at three points of cell cycle G1, G1/S and S
Proliferation and cell cycle HK2 cells divided slower than cells of cancerous cell lines (Caki-2, Caki-1)

Summary

Introduction

Triiodothyronine regulates proliferation acting as stimulator or inhibitor. P107 and p130 inhibits activity of cyclin/cdk complexes. Expression of all those proteins could be regulated by triiodothyronine. Thyroid hormone – triiodothyronine – regulates cells differentiation, proliferation and programmed death. Triiodothyronine acts both as an activator and inhibitor of cells proliferation [1]. Depending on type of TRE (thyroid hormone response elements) they could activate or inactivate transcription of TH regulated genes [2]. There are evidence that T3/TR negatively regulates E2F1 transcription [3] It has been reported TRβ receptors inhibits cells proliferation independently on triiodothyronine [4,5]

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Conclusion