title: Ultraviolet radiation down-regulates expression of the cell-cycle inhibitor p21WAF1/CIP1 in human cancer cells independently of p53.
abstract: OBJECTIVE
  To investigate the regulation of G1 cyclin-dependent kinase inhibitor p21WAF1/CIP1 by ultraviolet (UV) radiation in human carcinoma cells.
  
  
  METHODS
  Human cancer cell lines were irradiated with UV-C (254 nm) radiation, and their responses were characterized by Western blotting, Northern blotting, semi-quantitative RT-PCR analysis, trypan blue staining and flow cytometric cell cycle analysis.
  
  
  RESULTS
  At 24 h after UV irradiation, p21 expression was down-regulated in various cancer cell types (breast, prostrate, cervix, colon, glioma, squamous cancers), independently of their p53 genetic and functional status. UV-mediated down-regulation of p21 was dose- and time-dependent, was observed at the protein and mRNA levels, and did not correlate with cytotoxicity. Reduction of p21 protein levels required about 4 and 1 h, respectively, in MCF-7 and MDA-MB-231 breast cancer cells; some of the UV-induced decreases in p21 levels in these cell lines was due to enhanced proteasomal degradation. Despite decreased p21 levels, UV-irradiated breast cancer cells with wild-type p53 (MCF-7) retained the capacity for G1 cell-cycle arrest, whereas UV-treated cells with mutant p53 (MDA-MB-231) accumulated in S phase, suggesting a p53-dependent G1 checkpoint in MCF-7. UV treatment caused other alterations in cell-cycle regulatory, DNA repair and tumour suppressor genes, as described in this report.
  
  
  CONCLUSIONS
  In contrast to X-rays, UV causes down-regulation of the cell-cycle inhibitor p21 in tumour cells. It is postulated that this may be an adaptation to promote the growth and survival of transformed cells.
authors: Department of Radiation Oncology, Long Island Jewish Medical Center, Long Island Campus for the Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.
authors: J A
authors: JA
authors: Wang
authors: S
authors: S
authors: Fan
authors: R Q
authors: RQ
authors: Yuan
authors: Y X
authors: YX
authors: Ma
authors: Q
authors: Q
authors: Meng
authors: I D
authors: ID
authors: Goldberg
authors: E M
authors: EM
authors: Rosen
mesh_terms: D024682:BRCA2 Protein; D002453:Cell Cycle / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation / Q000528:radiation effects; D016193:G1 Phase / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects; D019398:Genes, BRCA1 / Q000528:radiation effects; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000528:radiation effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D014466:Ultraviolet Rays
chemical_list: D024682:BRCA2 Protein; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2