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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Telomerase induces immortalization of human esophageal keratinocytes without p16INK4a inactivation

Hideki Harada1, Hiroshi Nakagawa, Kenji Oyama

  • 1Gastroenterology Division, University of Pennsylvania, Philadelphia, PA 19104, USA.

Molecular Cancer Research : MCR
|August 27, 2003
PubMed

Insights

Restoring telomerase (hTERT) expression immortalized human esophageal keratinocytes without altering key cell cycle regulators. These cells remained responsive to senescence-inducing signals, suggesting telomerase is crucial for keratinocyte immortalization.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Normal human somatic cells have limited lifespans and undergo replicative senescence.
  • Telomere DNA erosion is a key factor in senescence, and its inhibition is crucial for cell immortalization and transformation.

Purpose of the Study:

  • To investigate the role of telomerase in the immortalization of human esophageal keratinocytes.
  • To determine if telomerase expression can overcome replicative senescence without inactivating critical tumor suppressor pathways.

Main Methods:

  • Restored expression of the catalytic subunit of telomerase (hTERT) in normal human esophageal epithelial cells (EPC2).
  • Assessed senescence, cell cycle regulation (p16INK4a/pRb and p53 pathways), and tumorigenic potential using organotypic culture.
  • Induced senescence via oncogenic H-ras or p16INK4a overexpression in immortalized cells.

Main Results:

  • EPC2 cells expressing hTERT (EPC2-hTERT) overcame senescence and became immortalized.
  • p16INK4a remained functional, and the p53 pathway was intact in immortalized EPC2-hTERT cells.
  • Immortalized cells exhibited basal cell hyperplasia in organotypic culture and could be induced to senesce by oncogene expression.

Conclusions:

  • Telomerase expression induces immortalization of human esophageal keratinocytes.
  • Immortalization occurs without inactivation of the p16INK4a/pRb or p53 pathways.
  • Telomerase is a critical factor for overcoming replicative senescence in esophageal keratinocytes.

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