Specific induction of gadd45 in human melanocytes and melanoma cells after UVB irradiation.
The purpose of our study was to analyze the p53-mediated response of human melanocytes and human melanoma cells to UVB (natural environmental carcinogen) or UVC irradiation (experimental carcinogen). A semi-quantitative RT-PCR method was developed to allow the analysis of the expression of 5 p53 effector genes (p21(WAF1), mdm2, cyclin G1, gadd45, bax) at the same time with a small amount of RNA (1 microg). In human melanocytic cells, the p53 downstream genes were found to be differentially activated after UVB and UVC irradiation. After UVB irradiation, p53 protein accumulation was sustained up to 48 hr that was not the case after UVC irradiation. Among the p53 effector genes tested, gadd45 was the only 1 to show a strong and specific induction after UVB irradiation. With high UVB doses, gadd45 was also the only gene to be transcribed. By contrast, after UVC irradiation, all the p53 effector genes tested were transcriptionally induced. Experiments conducted with fibroblasts and keratinocytes didn't show such a striking activation of gadd45 after UVB irradiation. These results point out the potential role of gadd45 in response to UVB irradiation in human melanocytes and the different p53-mediated responses to different carcinogens.
Pedeux
Rémy
R
INSERM U453, Lyon, France.
Lefort
Karine
K
Cuenin
Cyrille
C
Cortes
Ulrich
U
Kellner
Karine
K
Doré
Jean-François
JF
Nakazawa
Hisayoshi
H
D002478:Cells, Cultured; D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D014466:Ultraviolet Rays; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D000097642:GADD45 Proteins
D056746:Cyclin G; D056766:Cyclin G1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000097642:GADD45 Proteins; C494826:BAX protein, human; C534702:CCNG1 protein, human; C493956:CDKN1A protein, human; C497206:MDM2 protein, human