Regulation of Gadd45a mRNA expression in vascular smooth muscle under growth and stress conditions |
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| Authors: | Kettenhofen R Hoppe J Eberhard G Seul C Ko Y Sachinidis A |
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| Affiliation: | 1. Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France;2. National Cancer Institute, Vilnius, Lithuania;3. Department of Oncology, Herlev Hospital, Herlev;4. Department of Oncology, Aalborg University Hospital, Aalborg, Denmark;5. Department of Medical Oncology, Centre Georges François Leclerc, Dijon;6. INSERM, UMR1098, Besançon;7. Medicine, Centre Léon Bérard, Lyon, France;8. Department of Oncology & Hematology, Azienda University Hospital, Modena, Italy;9. Dana-Farber/Brigham and Women''s Cancer Center, Boston, USA;10. Department of Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain;11. Guy''s and St Thomas'' NHS Foundation Trust, London, UK;12. Department of General Medical Oncology, University Hospitals Leuven, Leuven;13. KU Leuven, Leuven, Belgium;14. Urocentrum, Prague, Czech Republic;15. General Oncology Department, Centre Oscar Lambret, Lille, France;16. Lithuanian University of Health Sciences Hospital, Kaunas, Lithuania;17. Gabinet Urologiczny, Gdynia, Gdańsk, Poland;18. Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy;19. Ipsen Innovation, Les Ulis, France;20. Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark |
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| Abstract: | In order to identify differentially expressed genes under growth conditions, quiescent vascular smooth muscle cells (VSMCs) were stimulated with foetal calf serum (FCS) or platelet-derived growth factor-BB (PDGF-BB) for different time periods. Analysing the gene expression by the differential display (DD) method, we identified the cDNA of the growth arrest and DNA damage inducible gene 45a (Gadd45a, also known as gadd45 and gadd45a). Treatment with FCS or PDGF-BB led to a transient down-regulating of Gadd45a expression during the G0/G1 phase and maximal expression when cells had completed division. We found that expression of p53 and BRCA1 mRNA precedes Gadd45a mRNA expression with a maximal induction in the S phase. As in smooth muscle cells, a similar pattern of the Gadd45a mRNA expression was observed in knockout Gadd45a(-/-) cultured mouse embryonic fibroblasts (MEFs). However, no differences between Gadd45a(+/+) and Gadd45a(-/-) cell lines were observed regarding their kinetics of cell division. These experiments suggest a function of Gadd45a when cells exit the cell cycle rather than when regulating the entry into the S phase. |
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