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Proc Natl Acad Sci U S A. Jun 25, 1996; 93(13): 6476–6481.

Telomerase activity in the regenerative basal layer of the epidermis inhuman skin and in immortal and carcinoma-derived skin keratinocytes.


Cellular senescence is defined by the limited proliferative capacity of normal cultured cells. Immortal cells overcome this regulation and proliferate indefinitively. One step in the immortalization process may be reactivation of telomerase activity, a ribonucleoprotein complex, which, by de novo synthesized telomeric TTAGGG repeats, can prevent shortening of the telomeres. Here we show that immortal human skin keratinocytes, irrespective of whether they were immortalized by simian virus 40, human papillomavirus 16, or spontaneously, as well as cell lines established from human skin squamous cell carcinomas exhibit telomerase activity. Unexpectedly, four of nine samples of intact human skin also were telomerase positive. By dissecting the skin we could show that the dermis and cultured dermal fibroblasts were telomerase negative. The epidermis and cultured skin keratinocytes, however, reproducibly exhibited enzyme activity. By separating different cell layers of the epidermis this telomerase activity could be assigned to the proliferative basal cells. Thus, in addition to hematopoietic cells, the epidermis, another example of a permanently regenerating human tissue, provides a further exception of the hypothesis that all normal human somatic tissues are telomerase deficient. Instead, these data suggest that in addition to contributing to the permanent proliferation capacity of immortal and tumor-derived keratinocytes, telomerase activity may also play a similar role in the lifetime regenerative capacity of normal epidermis in vivo.

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  • Pereira-Smith OM, Smith JR. Evidence for the recessive nature of cellular immortality. Science. 1983 Sep 2;221(4614):964–966. [PubMed]
  • Morin GB. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1989 Nov 3;59(3):521–529. [PubMed]
  • Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB, Bacchetti S. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 1992 May;11(5):1921–1929. [PMC free article] [PubMed]
  • Klingelhutz AJ, Barber SA, Smith PP, Dyer K, McDougall JK. Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells. Mol Cell Biol. 1994 Feb;14(2):961–969. [PMC free article] [PubMed]
  • Counter CM, Hirte HW, Bacchetti S, Harley CB. Telomerase activity in human ovarian carcinoma. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2900–2904. [PMC free article] [PubMed]
  • Nilsson P, Mehle C, Remes K, Roos G. Telomerase activity in vivo in human malignant hematopoietic cells. Oncogene. 1994 Oct;9(10):3043–3048. [PubMed]
  • Rhyu MS. Telomeres, telomerase, and immortality. J Natl Cancer Inst. 1995 Jun 21;87(12):884–894. [PubMed]
  • Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985 Dec;43(2 Pt 1):405–413. [PubMed]
  • Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature. 1989 Jan 26;337(6205):331–337. [PubMed]
  • Harley CB. Telomere loss: mitotic clock or genetic time bomb? Mutat Res. 1991 Mar-Nov;256(2-6):271–282. [PubMed]
  • Harley CB, Vaziri H, Counter CM, Allsopp RC. The telomere hypothesis of cellular aging. Exp Gerontol. 1992 Jul-Aug;27(4):375–382. [PubMed]
  • Counter CM, Gupta J, Harley CB, Leber B, Bacchetti S. Telomerase activity in normal leukocytes and in hematologic malignancies. Blood. 1995 May 1;85(9):2315–2320. [PubMed]
  • Broccoli D, Young JW, de Lange T. Telomerase activity in normal and malignant hematopoietic cells. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9082–9086. [PMC free article] [PubMed]
  • Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, Piatyszek MA, Shay JW, Ishioka S, Yamakido M. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol. 1995 Oct 15;155(8):3711–3715. [PubMed]
  • Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994 Dec 23;266(5193):2011–2015. [PubMed]
  • Allsopp RC, Harley CB. Evidence for a critical telomere length in senescent human fibroblasts. Exp Cell Res. 1995 Jul;219(1):130–136. [PubMed]
  • Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol. 1988 Mar;106(3):761–771. [PMC free article] [PubMed]
  • Baden HP, Kubilus J, Wolman SR, Steinberg ML, Phillips SB, Kvedar JC. NM1 keratinocyte line is cytogenetically and biologically stable and exhibits a unique structural protein. J Invest Dermatol. 1987 Dec;89(6):574–579. [PubMed]
  • Taylor-Papadimitriou J, Purkis P, Lane EB, McKay IA, Chang SE. Effects of SV40 transformation on the cytoskeleton and behavioural properties of human keratinocytes. Cell Differ. 1982 May;11(3):169–180. [PubMed]
  • Dürst M, Dzarlieva-Petrusevska RT, Boukamp P, Fusenig NE, Gissmann L. Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene. 1987;1(3):251–256. [PubMed]
  • Dürst M, Gallahan D, Jay G, Rhim JS. Glucocorticoid-enhanced neoplastic transformation of human keratinocytes by human papillomavirus type 16 and an activated ras oncogene. Virology. 1989 Dec;173(2):767–771. [PubMed]
  • Boukamp P, Tilgen W, Dzarlieva RT, Breitkreutz D, Haag D, Riehl RK, Bohnert A, Fusenig NE. Phenotypic and genotypic characteristics of a cell line from a squamous cell carcinoma of human skin. J Natl Cancer Inst. 1982 Mar;68(3):415–427. [PubMed]
  • Tilgen W, Boukamp P, Breitkreutz D, Dzarlieva RT, Engstner M, Haag D, Fusenig NE. Preservation of morphological, functional, and karyotypic traits during long-term culture and in vivo passage of two human skin squamous cell carcinomas. Cancer Res. 1983 Dec;43(12 Pt 1):5995–6011. [PubMed]
  • Rheinwald JG, Beckett MA. Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res. 1981 May;41(5):1657–1663. [PubMed]
  • Jones PH, Harper S, Watt FM. Stem cell patterning and fate in human epidermis. Cell. 1995 Jan 13;80(1):83–93. [PubMed]
  • Shay JW, Tomlinson G, Piatyszek MA, Gollahon LS. Spontaneous in vitro immortalization of breast epithelial cells from a patient with Li-Fraumeni syndrome. Mol Cell Biol. 1995 Jan;15(1):425–432. [PMC free article] [PubMed]
  • Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J. 1995 Sep 1;14(17):4240–4248. [PMC free article] [PubMed]
  • Lindsey J, McGill NI, Lindsey LA, Green DK, Cooke HJ. In vivo loss of telomeric repeats with age in humans. Mutat Res. 1991 Jan;256(1):45–48. [PubMed]
  • Chadeneau C, Hay K, Hirte HW, Gallinger S, Bacchetti S. Telomerase activity associated with acquisition of malignancy in human colorectal cancer. Cancer Res. 1995 Jun 15;55(12):2533–2536. [PubMed]
  • Cairns J. Mutation selection and the natural history of cancer. Nature. 1975 May 15;255(5505):197–200. [PubMed]

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