p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts

  • Authors:
    • Wenqi Chen
    • Jian Kang
    • Jiping Xia
    • Yanhua li
    • Bo Yang
    • Bin Chen
    • Weiling Sun
    • Xiuzu Song
    • Wenzhong Xiang
    • Xiaoyong Wang
    • Fei Wang
    • Yinsheng Wan
    • Zhigang Bi
  • View Affiliations

  • Published online on: May 1, 2008     https://doi.org/10.3892/ijmm.21.5.645
  • Pages: 645-653
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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 β-galactosidase (SA β-gal) activity, growth arrest, and the overexpression of senescence-associated genes. Firstly, there was an increase in the proportion of cells positive for SA β-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, p21WAF-1 and p16INK-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-1α 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.

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May 2008
Volume 21 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chen W, Kang J, Xia J, li Y, Yang B, Chen B, Sun W, Song X, Xiang W, Wang X, Wang X, et al: p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts. Int J Mol Med 21: 645-653, 2008.
APA
Chen, W., Kang, J., Xia, J., li, Y., Yang, B., Chen, B. ... Bi, Z. (2008). p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts. International Journal of Molecular Medicine, 21, 645-653. https://doi.org/10.3892/ijmm.21.5.645
MLA
Chen, W., Kang, J., Xia, J., li, Y., Yang, B., Chen, B., Sun, W., Song, X., Xiang, W., Wang, X., Wang, F., Wan, Y., Bi, Z."p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts". International Journal of Molecular Medicine 21.5 (2008): 645-653.
Chicago
Chen, W., Kang, J., Xia, J., li, Y., Yang, B., Chen, B., Sun, W., Song, X., Xiang, W., Wang, X., Wang, F., Wan, Y., Bi, Z."p53-related apoptosis resistance and tumor suppression activity in UVB-induced premature senescent human skin fibroblasts". International Journal of Molecular Medicine 21, no. 5 (2008): 645-653. https://doi.org/10.3892/ijmm.21.5.645