title: p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts.
abstract: Chronic exposure to solar UV irradiation leads to photoaging, immunosuppression, and ultimately carcinogenesis. Cellular senescence is thought to play an important role in tumor suppression and apoptosis resistance. However, the relationships among stress-induced premature senescence (SIPS), tumorigenesis and apoptosis induced by UVB remain unknown. We developed a model of UVB-induced premature senescence in human skin fibroblasts (HSFs). After five repeated subcytotoxic UVB exposures at a dose of 10 mJ/cm2, the following biomarkers of senescence were markedly present: senescence-associated beta-galactosidase (SA beta-gal) activity, growth arrest, and the overexpression of senescence-associated genes. Firstly, there was an increase in the proportion of cells positive for SA beta-gal activity. Secondly, there was a loss of replicative potential as assessed by MTT assay. FACS analysis showed that UVB-stressed HSFs were blocked mostly in the G1 phase of the cell cycle, and replicative senescence, and protein expression of p53, p21(WAF-1) and p16(INK-4a) increased significantly. Thirdly, the mRNA levels of three senescence-associated genes, fibronectin, osteonectin and SM22, also increased. A real time PCR array to investigate the mRNA expression of p53-related genes involved in growth arrest, apoptosis and tumorigenesis indicated that p53, p21, p19, Hdm2, and Bax were up-regulated, and bcl, HIF-1alpha and VEGF were down-regulated. Collectively, our data suggest that UVB-induced SIPS plays an important role in p53-related apoptosis resistance and tumor suppression activity.
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Jiping
authors.initials: J
authors.lastname: Xia
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Weiling
authors.initials: W
authors.lastname: Sun
authors.forename: Xiuzu
authors.initials: X
authors.lastname: Song
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Xiang
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wan
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Bi
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D012867:Skin / Q000166:cytology / Q000528:radiation effects; D015595:Skin Aging; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D015415:Biomarkers; D016159:Tumor Suppressor Protein p53