Mechanism of telomerase repression during terminal differentiation of normal epithelial cells and squamous carcinoma lines

  • Authors:
    • David L. Crowe
    • Dan C. Nguyen
    • Arthur Ohannessian
  • View Affiliations

  • Published online on: September 1, 2005     https://doi.org/10.3892/ijo.27.3.847
  • Pages: 847-854
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Abstract

Stratified squamous epithelial cells undergo an orderly process of cell cycle arrest following detachment from the basement membrane. The basal layer cells which adhere to the basement membrane express telomerase, which maintains the ends of chromosomes in this rapidly dividing population. Non-dividing suprabasal cells downregulate telomerase activity. However, the mechanisms regulating this inhibition are unknown. We examined the regulation of telomerase expression in anchorage-deprived normal human epidermal keratinocytes and squamous cell carcinoma lines. Anchorage-deprived cells underwent rapid loss of telomerase activity. Attachment loss was associated with increased ERK1 activity, G1 to S phase progression, and subsequent G2 arrest. Adhesion to collagen via specific integrin subunits inhibited ERK1 activity and telomerase repression. Loss of telomerase expression was associated with recruitment of an Rb/HDAC1 repressor complex to the -98 E2F site of the hTERT promoter. We propose a mechanism by which anchorage deprivation inhibits telomerase activity in stratified squamous epithelial cells and squamous cell carcinoma lines.

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September 2005
Volume 27 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Crowe DL, Nguyen DC and Ohannessian A: Mechanism of telomerase repression during terminal differentiation of normal epithelial cells and squamous carcinoma lines. Int J Oncol 27: 847-854, 2005.
APA
Crowe, D.L., Nguyen, D.C., & Ohannessian, A. (2005). Mechanism of telomerase repression during terminal differentiation of normal epithelial cells and squamous carcinoma lines. International Journal of Oncology, 27, 847-854. https://doi.org/10.3892/ijo.27.3.847
MLA
Crowe, D. L., Nguyen, D. C., Ohannessian, A."Mechanism of telomerase repression during terminal differentiation of normal epithelial cells and squamous carcinoma lines". International Journal of Oncology 27.3 (2005): 847-854.
Chicago
Crowe, D. L., Nguyen, D. C., Ohannessian, A."Mechanism of telomerase repression during terminal differentiation of normal epithelial cells and squamous carcinoma lines". International Journal of Oncology 27, no. 3 (2005): 847-854. https://doi.org/10.3892/ijo.27.3.847