Table of Contents Author Guidelines Submit a Manuscript
Biochemistry Research International
Volume 2012, Article ID 951574, 8 pages
http://dx.doi.org/10.1155/2012/951574
Review Article

Role of in Replicative Senescence and DNA Damage-Induced Premature Senescence in p53-Deficient Human Cells

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada T6G 1Z2

Received 19 May 2012; Accepted 21 June 2012

Academic Editor: Mandi M. Murph

Copyright © 2012 Razmik Mirzayans et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. I. Huschtscha and R. R. Reddel, “p16INK4a and the control of cellular proliferative life span,” Carcinogenesis, vol. 20, no. 6, pp. 921–926, 1999. View at Publisher · View at Google Scholar · View at Scopus
  2. U. Herbig, W. A. Jobling, B. P. C. Chen, D. J. Chen, and J. M. Sedivy, “Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a,” Molecular Cell, vol. 14, no. 4, pp. 501–513, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Zhang, “Molecular signaling and genetic pathways of senescence: its role in tumorigenesis and aging,” Journal of Cellular Physiology, vol. 210, no. 3, pp. 567–574, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Vergel and A. Carnero, “Bypassing cellular senescence by genetic screening tools,” Clinical and Translational Oncology, vol. 12, no. 6, pp. 410–417, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Rajaraman, D. L. Guernsey, M. M. Rajaraman, and S. R. Rajaraman, “Stem cells, senescence, neosis and self-renewal in cancer,” Cell Biology International, vol. 29, no. 12, pp. 1084–1097, 2005. View at Google Scholar · View at Scopus
  6. R. Mirzayans, B. Andrais, A. Scott, and D. Murray, “New insights into p53 signaling and cancer-cell response to DNA damage: implications for cancer therapy,” Journal of Biomedicine and Biotechnology, vol. 2012, Article ID 170325, 16 pages, 2012. View at Publisher · View at Google Scholar
  7. R. Mirzayans and D. Murray, “Cellular senescence: implications for cancer therapy,” in New Research on Cell Aging, R. B. Garvey, Ed., pp. 1–64, Nova Science, New York, NY, USA, 2007. View at Google Scholar
  8. C. M. Beauséjour, A. Krtolica, F. Galimi et al., “Reversal of human cellular senescence: roles of the p53 and p16 pathways,” The EMBO Journal, vol. 22, no. 16, pp. 4212–4222, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. I. B. Roninson, “Tumor cell senescence in cancer treatment,” Cancer Research, vol. 63, no. 11, pp. 2705–2715, 2003. View at Google Scholar · View at Scopus
  10. K. Itahana, Y. Zou, Y. Itahana et al., “Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1,” Molecular and Cellular Biology, vol. 23, no. 1, pp. 389–401, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Chen, X. Huang, D. Halicka et al., “Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53,” American Journal of Physiology, vol. 290, no. 4, pp. H1575–H1586, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Kunieda, T. Minamino, J. I. Nishi et al., “Angiotensin II induces premature senescence of vascular smooth muscle cells and accelerates the development of atherosclerosis via a p21-dependent pathway,” Circulation, vol. 114, no. 9, pp. 953–960, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. E. V. Sviderskaya, V. C. Gray-Schopfer, S. P. Hill et al., “p16/cyclin-dependent kinase inhibitor 2A deficiency in human melanocyte senescence, apoptosis, and immortalization: possible implications for melanoma progression,” Journal of the National Cancer Institute, vol. 95, no. 10, pp. 723–732, 2003. View at Google Scholar · View at Scopus
  14. D. A. Freedman and J. Folkman, “CDK2 translational down-regulation during endothelial senescence,” Experimental Cell Research, vol. 307, no. 1, pp. 118–130, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. K. D. Robertson and P. A. Jones, “Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locus,” Oncogene, vol. 18, no. 26, pp. 3810–3820, 1999. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Ortega, M. Malumbres, and M. Barbacid, “Cyclin D-dependent kinases, INK4 inhibitors and cancer,” Biochimica et Biophysica Acta, vol. 1602, no. 1, pp. 73–87, 2002. View at Publisher · View at Google Scholar · View at Scopus
  17. J. J. L. Jacobs and T. de Lange, “p16INK4a as a second effector of the telomere damage pathway,” Cell Cycle, vol. 4, no. 10, pp. 1364–1368, 2005. View at Google Scholar · View at Scopus
  18. J. J. L. Jacobs, P. Keblusek, E. Robanus-Maandag et al., “Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancers,” Nature Genetics, vol. 26, no. 3, pp. 291–299, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. J. Gil, D. Bernard, D. Martínez, and D. Beach, “Polycomb CBX7 has a unifying role in cellular lifespan,” Nature Cell Biology, vol. 6, no. 1, pp. 67–72, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. J. L. Jacobs, K. Kieboom, S. Marino, R. A. DePinho, and M. van Lohuizen, “The oncogene and polycombgroup gene bmi-1 regulates cell proliferation and senescence through the ink4a locus,” Nature, vol. 397, no. 6715, pp. 164–168, 1999. View at Publisher · View at Google Scholar · View at Scopus
  21. J. W. Jung, S. Lee, M. S. Seo et al., “Histone deacetylase controls adult stem cell aging by balancing the expression of polycomb genes and jumonji domain containing 3,” Cellular and Molecular Life Sciences, vol. 67, no. 7, pp. 1165–1176, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Feng, X. Wang, L. Xu et al., “The transcription factor ZBP-89 suppresses p16 expression through a histone modification mechanism to affect cell senescence,” FEBS Journal, vol. 276, no. 15, pp. 4197–4206, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. H. Rayess, M. B. Wang, and E. S. Srivatsan, “Cellular senescence and tumor suppressor gene p16,” International Journal of Cancer, vol. 130, no. 8, pp. 1715–1725, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Hernández-Vargas, E. Ballestar, P. Carmona-Saez et al., “Transcriptional profiling of MCF7 breast cancer cells in response to 5-fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53,” International Journal of Cancer, vol. 119, no. 5, pp. 1164–1175, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. R. M. Alani, A. Z. Young, and C. B. Shifflett, “Id1 regulation of cellular senescence through transcriptional repression of p16/Ink4a,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 14, pp. 7812–7816, 2001. View at Publisher · View at Google Scholar · View at Scopus
  26. D. Polsky, A. Z. Young, K. J. Busam, and R. M. Alani, “The transcriptional repressor of p16/Ink4a, Id1, is up-regulated in early melanomas,” Cancer Research, vol. 61, no. 16, pp. 6008–6011, 2001. View at Google Scholar · View at Scopus
  27. W. F. Leong, J. F. L. Chau, and B. Li, “p53 deficiency leads to compensatory up-regulation of p16INK4a,” Molecular Cancer Research, vol. 7, no. 3, pp. 354–360, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Serrano, G. J. Hannon, and D. Beach, “A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4,” Nature, vol. 366, no. 6456, pp. 704–707, 1993. View at Publisher · View at Google Scholar · View at Scopus
  29. D. Parry, S. Bates, D. J. Mann, and G. Peters, “Lack of cyclin D-Cdk complexes in Rb-negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product,” The EMBO Journal, vol. 14, no. 3, pp. 503–511, 1995. View at Google Scholar · View at Scopus
  30. C. J. Sherr and F. McCormick, “The RB and p53 pathways in cancer,” Cancer Cell, vol. 2, no. 2, pp. 103–112, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Harada, K. Nakagavva, S. Iwata et al., “Restoration of wild-type p16 down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in human gliomas,” Cancer Research, vol. 59, no. 15, pp. 3783–3789, 1999. View at Google Scholar · View at Scopus
  32. M. Castellano, P. M. Pollock, M. K. Walters et al., “CDKN2A/p16 is inactivated in most melanoma cell lines,” Cancer Research, vol. 57, no. 21, pp. 4868–4875, 1997. View at Google Scholar · View at Scopus
  33. R. Fåhraeus and D. P. Lane, “The p16INK4a tumour suppressor protein inhibits αvβ3 integrin-mediated cell spreading on vitronectin by blocking PKC-dependent localization of αvβ3 to focal contacts,” The EMBO Journal, vol. 18, no. 8, pp. 2106–2118, 1999. View at Google Scholar · View at Scopus
  34. P. J. Vojta and J. C. Barrett, “Genetic analysis of cellular senescence,” Biochimica et Biophysica Acta, vol. 1242, no. 1, pp. 29–41, 1995. View at Publisher · View at Google Scholar · View at Scopus
  35. V. Sandig, K. Brand, S. Herwig, J. Lukas, J. Bartek, and M. Strauss, “Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to induce apoptotic tumor cell death,” Nature Medicine, vol. 3, no. 3, pp. 313–319, 1997. View at Publisher · View at Google Scholar · View at Scopus
  36. I. Naruse, Y. Heike, S. Hama, M. Mori, and N. Saijo, “High concentrations of recombinant adenovirus expressing p16INK4a gene induces apoptosis in lung cancer cell lines,” Anticancer Research, vol. 18, no. 6 A, pp. 4275–4282, 1998. View at Google Scholar · View at Scopus
  37. T. Plath, K. Detjen, M. Welzel et al., “A novel function for the tumor suppressor p16INK4a: induction of anoikis via upregulation of the α5β1 fibronectin receptor,” Journal of Cell Biology, vol. 150, no. 6, pp. 1467–1477, 2000. View at Publisher · View at Google Scholar · View at Scopus
  38. B. Wolff and M. Naumann, “INK4 cell cycle inhibitors direct transcriptional inactivation of NF-κB,” Oncogene, vol. 18, no. 16, pp. 2663–2666, 1999. View at Publisher · View at Google Scholar · View at Scopus
  39. X. Fang, X. Jin, H. J. Xu et al., “Expression of p16 induces transcriptional downregulation of the RB gene,” Oncogene, vol. 16, no. 1, pp. 1–8, 1998. View at Google Scholar · View at Scopus
  40. L. I. Huschtscha, J. D. Moore, J. R. Noble et al., “Normal human mammary epithelial cells proliferate rapidly in the presence of elevated levels of the tumor suppressors p53 and p21WAF1/CIP1,” Journal of Cell Science, vol. 122, no. 16, pp. 2989–2995, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. H. Hu, Z. Li, J. Chen et al., “P16 reactivation induces anoikis and exhibits antitumour potency by downregulating Akt/survivin signalling in hepatocellular carcinoma cells,” Gut, vol. 60, no. 5, pp. 710–721, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. R. Mirzayans, B. Andrais, A. Scott, M. C. Paterson, and D. Murray, “Single-cell analysis of p16INK4a and p21WAF1 expression suggests distinct mechanisms of senescence in normal human and Li-Fraumeni syndrome fibroblasts,” Journal of Cellular Physiology, vol. 223, no. 1, pp. 57–67, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. M. A. Al-Mohanna, P. S. Manogaran, Z. Al-Mukhalafi, K. A. Al-Hussein, and A. Aboussekhra, “The tumor suppressor p16INK4a gene is a regulator of apoptosis induced by ultraviolet light and cisplatin,” Oncogene, vol. 23, no. 1, pp. 201–212, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. D. Zhang, T. Shimizu, N. Araki et al., “Aurora A overexpression induces cellular senescence in mammary gland hyperplastic tumors developed in p53-deficient mice,” Oncogene, vol. 27, no. 31, pp. 4305–4314, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Yamakoshi, A. Takahashi, F. Hirota et al., “Real-time in vivo imaging of p16INK4a reveals cross talk with p53,” Journal of Cell Biology, vol. 186, no. 3, pp. 393–407, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. D. A. Alcorta, Y. Xiong, D. Phelps, G. Hannon, D. Beach, and J. C. Barrett, “Involvement of the cyclin-dependent kinase inhibitor p16INK4a in replicative senescence of normal human fibroblasts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 24, pp. 13742–13747, 1996. View at Publisher · View at Google Scholar · View at Scopus
  47. G. H. Stein, L. F. Drullinger, A. Soulard, and V. Dulić, “Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts,” Molecular and Cellular Biology, vol. 19, no. 3, pp. 2109–2117, 1999. View at Google Scholar · View at Scopus
  48. S. Brookes, J. Rowe, A. Gutierrez Del Arroyo, J. Bond, and G. Peters, “Contribution of p16INK4a to replicative senescence of human fibroblasts,” Experimental Cell Research, vol. 298, no. 2, pp. 549–559, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. E. T. Cánepa, M. E. Scassa, J. M. Ceruti et al., “INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions,” IUBMB Life, vol. 59, no. 7, pp. 419–426, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. R. D. C. Barley, L. Enns, M. C. Paterson, and R. Mirzayans, “Aberrant p21WAF1-dependent growth arrest as the possible mechanism of abnormal resistance to ultraviolet light cytotoxicity in Li-Fraumeni syndrome fibroblast strains heterozygous for TP53 mutations,” Oncogene, vol. 17, no. 5, pp. 533–543, 1998. View at Google Scholar · View at Scopus
  51. R. Mirzayans, D. Severin, and D. Murray, “Relationship between DNA double-strand break rejoining and cell survival after exposure to ionizing radiation in human fibroblast strains with differing ATM/p53 status: implications for evaluation of clinical radiosensitivity,” International Journal of Radiation Oncology Biology Physics, vol. 66, no. 5, pp. 1498–1505, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. H. Vaziri, M. D. West, R. C. Allsopp et al., “ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase,” The EMBO Journal, vol. 16, no. 19, pp. 6018–6033, 1997. View at Publisher · View at Google Scholar · View at Scopus
  53. R. Mirzayans, A. Scott, B. Andrais, S. Pollock, and D. Murray, “Ultraviolet light exposure triggers nuclear accumulation of p21WAF1 and accelerated senescence in human normal and nucleotide excision repair-deficient fibroblast strains,” Journal of Cellular Physiology, vol. 215, no. 1, pp. 55–67, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. T. Nobori, K. Miura, D. J. Wu, A. Lois, K. Takabayashi, and D. A. Carson, “Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers,” Nature, vol. 368, no. 6473, pp. 753–756, 1994. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Kamb, N. A. Gruis, J. Weaver-Feldhaus et al., “A cell cycle regulator potentially involved in genesis of many tumor types,” Science, vol. 264, no. 5157, pp. 436–440, 1994. View at Google Scholar · View at Scopus
  56. C. H. Spruck 3rd, M. Gonzalez-Zulueta, A. Shibata et al., “p16 gene in uncultured tumours,” Nature, vol. 370, no. 6486, pp. 183–184, 1994. View at Publisher · View at Google Scholar · View at Scopus
  57. B. D. Chang, E. V. Broude, M. Dokmanovic et al., “A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents,” Cancer Research, vol. 59, no. 15, pp. 3761–3767, 1999. View at Google Scholar · View at Scopus
  58. R. Mirzayans, A. Scott, M. Cameron, and D. Murray, “Induction of accelerated senescence by γ radiation in human solid tumor-derived cell lines expressing wild-type TP53,” Radiation Research, vol. 163, no. 1, pp. 53–62, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. S. K. Myöhänen, S. B. Baylin, and J. G. Herman, “Hypermethylation can selectively silence individual p16INK4A alleles in neoplasia,” Cancer Research, vol. 58, no. 4, pp. 591–593, 1998. View at Google Scholar · View at Scopus
  60. W. Zhang, J. Zhu, J. Bai et al., “Comparison of the inhibitory effects of three transcriptional variants of CDKN2A in human lung cancer cell line A549,” Journal of Experimental and Clinical Cancer Research, vol. 29, no. 1, article 74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. K. R. Jones, L. W. Elmore, C. Jackson-Cook et al., “p53-dependent accelerated senescence induced by ionizing radiation in breast tumour cells,” International Journal of Radiation Biology, vol. 81, no. 6, pp. 445–458, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Wang, F. Morsbach, D. Sander et al., “EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks,” Cancer Research, vol. 71, no. 19, pp. 6261–6269, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. J. A. Reed, F. Loganzo, C. R. Shea et al., “Loss of expression of the p16/cyclin-dependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression,” Cancer Research, vol. 55, no. 13, pp. 2713–2718, 1995. View at Google Scholar · View at Scopus
  64. Z. Y. Abd Elmageed, R. L. Gaur, M. Williams et al., “Characterization of coordinated immediate responses by p16INK4a and p53 pathways in UVB-irradiated human skin cells,” The Journal of Investigative Dermatology, vol. 129, no. 1, pp. 175–183, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Hollestelle, J. H. A. Nagel, M. Smid et al., “Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines,” Breast Cancer Research and Treatment, vol. 121, no. 1, pp. 53–64, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. C. M. Galmarini, N. Falette, E. Tabone et al., “Inactivation of wild-type p53 by a dominant negative mutant renders MCF-7 cells resistant to tubulin-binding agent cytotoxicity,” British Journal of Cancer, vol. 85, no. 6, pp. 902–908, 2001. View at Publisher · View at Google Scholar · View at Scopus
  67. E. A. Ostrakhovitch, P. E. Olsson, J. Von Hofsten, and M. G. Cherian, “P53 mediated regulation of metallothionein transcription in breast cancer cells,” Journal of Cellular Biochemistry, vol. 102, no. 6, pp. 1571–1583, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. S. J. Robles and G. R. Adami, “Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the premature senescence of normal fibroblasts,” Oncogene, vol. 16, no. 9, pp. 1113–1123, 1998. View at Google Scholar · View at Scopus