Regulation of Gadd45a mRNA expression in vascular smooth muscle under growth and stress conditions.
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.
Kettenhofen
R
R
Medizinische Universitäts-Poliklinik, Wilhelmstrasse 35-37, D-53111, Bonn, Germany.
Hoppe
J
J
Eberhard
G
G
Seul
C
C
Ko
Y
Y
Sachinidis
A
A
D000818:Animals; D017209:Apoptosis; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D000077214:Becaplermin; D002453:Cell Cycle; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D000097642:GADD45 Proteins
D019313:BRCA1 Protein; D000077214:Becaplermin; D003470:Culture Media; D047908:Intracellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins