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Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse

Oncogene volume 18, pages 1297–1302 (1999)Cite this article

Abstract

Telomerase is a ribonucleoprotein enzyme that adds hexanucleotide repeats TTAGGG to the ends of chromosomes. Telomerase activation is known to play a crucial role in cell-immortalization and carcinogenesis. Telomerase is shown to have a correlation with cell cycle progression, which is controlled by the regulation of cyclins, cyclin dependent kinases (cdks) and cyclin dependent kinase inhibitors (cdkis). Abnormal expression of these regulatory molecules may cause alterations in cell cycle with uncontrolled cell growth, a universal feature of neoplasia. Skin cancer is the most prevalent form of cancer in humans and the solar UV radiation is its major cause. Here, we investigated modulation in telomerase activity and protein expression of cell cycle regulatory molecules during the development of UVB-induced tumors in SKH-1 hairless mice. The mice were exposed to 180 mjoules/cm2 UVB radiation, thrice weekly for 24 weeks. The animals were sacrificed at 4 week intervals and the studies were performed in epidermis. Telomerase activity was barely detectable in the epidermis of non-irradiated mouse. UVB exposure resulted in a progressive increase in telomerase activity starting from the 4th week of exposure. The increased telomerase activity either persisted or further increased with the increased exposure. In papillomas and carcinomas the enzyme activity was comparable and was 45-fold higher than in the epidermis of control mice. Western blot analysis showed an upregulation in the protein expression of cyclin D1 and cyclin E and their regulatory subunits cdk4 and cdk2 during the course of UVB exposure and in papillomas and carcinomas. The protein expression of cdk6 and ckis viz. p16/Ink4A, p21/Waf1 and p27/Kip1 did not show any significant change in UVB exposed skin, but significant upregulation was observed both in papillomas and carcinomas. The results suggest that telomerase activation may be involved in UVB-induced tumorigenesis in mouse skin and that increased telomerase activity may be associated with G1 phase of the cell cycle.

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Acknowledgements

This work was supported by US Public Health Service Grants R01 CA 51802, P01 CA 48735, P30 CA 43703 and P30 AR 39750.

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  1. Sivaprakasam Balasubramanian

    Present address: Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 2109 Abington Road, Cleveland, Ohio, 44106, USA

  2. Ki-Ho Kim

    Present address: Department of Dermatology, Dong-A University Hospital and College of Medicine, #1 DongDaeshin3-Dong, Seo-Ku, Pusan, 602-103, Korea

Authors and Affiliations

  1. Department of Dermatology, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, 44106, Ohio, USA

    Sivaprakasam Balasubramanian, Ki-Ho Kim, Nihal Ahmad & Hasan Mukhtar

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Balasubramanian, S., Kim, KH., Ahmad, N. et al. Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. Oncogene 18, 1297–1302 (1999). https://doi.org/10.1038/sj.onc.1202417

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