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Telomerase in human development and cancer

J W Shay1

  • 1Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center at Dallas 75235, USA.

Journal of Cellular Physiology
|November 20, 1997
PubMed
Summary

Cellular immortalization, a key step in cancer, involves inactivating tumor suppressors and reactivating telomerase. This enzyme maintains telomeres, compensating for losses during cell division and is upregulated in most human cancers.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cellular immortalization is a critical step in cancer progression, enabling indefinite proliferation.
  • This process requires overcoming specific cellular mechanisms, including the inactivation of tumor suppressor pathways (p53 and pRB).
  • Reactivation of the enzyme telomerase is consistently observed in nearly 90% of human cancers.

Purpose of the Study:

  • To review the telomere-telomerase theory concerning aging and cancer.
  • To elucidate the roles of telomerase in human development, cellular differentiation, and cancer.
  • To explore the potential of targeting telomerase for cancer diagnosis and therapeutics.

Main Methods:

  • Review of existing literature on telomere biology and telomerase function.
  • Analysis of telomerase expression patterns across human development, differentiation, and various cancer types.
  • Examination of the mechanistic link between telomere maintenance and cellular immortalization.

Main Results:

  • Telomerase synthesizes repetitive sequences (TTAGGG) at telomere ends, preventing shortening with each cell division.
  • While active in embryonic tissues, telomerase is typically undetectable in most adult somatic tissues.
  • Upregulation or reactivation of telomerase is a near-universal event in human tumorigenesis.

Conclusions:

  • The telomere-telomerase theory provides a framework for understanding cellular aging and cancer development.
  • Understanding telomerase regulation is crucial for developing novel cancer diagnostics and therapeutics.
  • Targeting telomerase presents a promising strategy for future anti-cancer treatments.

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