Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 374, Issue 1-2, Pages 10-21Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2013.03.026
Keywords
TRPC2; Calcium; Proliferation; Physiology; MMP2; Invasion
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Funding
- Academy of Finland
- Sigrid Juselius Foundation
- Centre of Excellence in Cell Stress and Molecular Ageing (Abo Akademi University)
- Magnus Ehrnrooth Foundation
- Receptor Research Program (Abo Akademi University and University of Turku)
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Mammalian transient receptor potential (TRP) channels are involved in many physiologically important processes. Here, we have studied the significance of the TRPC2 channel in the regulation of rat thyroid FRTL-5 cell proliferation, migration, adhesion and invasion, using stable TRPC2 (shTRPC2) knock-down cells. In the shTRPC2 cells, proliferation was decreased due to a prolonged G1/S cell cycle phase. The tumor suppressor p53 and the cyclin-dependant kinase inhibitors p27 and p21 were upregulated. Cell invasion, adhesion and migration were also attenuated in shTRPC2 cells, probably due to decreased activity of both Rac and calpain, and a decreased secretion and activity of matrix metalloproteinase 2. The. attenuated proliferation, migration, invasion and ATP-evoked calcium entry was mimicked by over-expressing a non-conducting, truncated TRPC2 (TRPC2-DN) in wild type cells, and was reversed by overexpression of TRPC2-GFP in shTRPC2 cells. In conclusion, TRPC2 is an important regulator of rat thyroid. cell function. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
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