Telomeres and Telomerase in Cancer

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Telomeres and Telomerase in Cancer

• By Tara Lynn

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What is a telomere?

• A telomere is the end structure of a chromosome.
• Telomeres are essential regulators of both cell
  life span and chromosomal integrity.

jshay_at_mednet.swmed.edu, University of Texas,
Southwestern Medical Center
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Why do we need telomeres?
Telomerase Demo created by Dr. Donald F. Slish at
SUNY, Plattsburgh
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What is the structure of a telomere?

• All telomeres are composed of large arrays of
  short guanine-rich sequences, such as those found
  in mammalian cells, 5-TTAGGGG-3. (Hahn. Journal
  of Clinical Oncology, vol21, no10, pp2034-2043)

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Structure of Telomere
http//www.erin.utoronto.ca/w3bio/JBC372/lecture0
6_2004/sld035.htm
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• Telomeres in embryonic cells, germ cells, and
  cells that require extended regenerations are
  long.
• All other cells have short telomeres.
• With each cell division telomeres become
  shorter, until after dozens of divisions
  telomeres get lost and the cell eventually dies.
  (Bodnar et al. (1998) Science 279, 349-352).

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What is Telomerase?

• In the germ line and in rapidly dividing somatic
  cells, telomerase, a reverse transcriptase that
  contains an RNA template, adds TTAGGG repeats to
  chromosome ends. Lodish et. al.
• Telomerase is detectable in the majority of
  cancer cell lines and tumors.

jshay_at_mednet.swmed.edu, University of Texas,
Southwestern Medical Center
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Telomeres and Telomerase can both suppress and
cause cancer.
Telomere Loss
Telomerase Activation
Tumor Suppression Limits cell lifespan (telomeres long) Protects chromosome ends (?)
Tumor Promotion Induces genomic instability (telomeres short) Promotes immortalization
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What happens to an organism with dysfunctional
telomerase?

• The results are mixed

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Option 1 defects and aging

• Progressive defects in cells with high turnover
  (immune, hematopoietic, and reproductive organs)
  in knock out mice. Nature April 9, 1998
• Dyskeratosis congenita in humans premature organ
  failure, cancer predisposition (Hahn 2003)

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Option 2 Nothing happens for several generations

• After five or six generations, telomere loss in
  mice leads to sterility. (Greider 1997)
• mice that lack telomerase activity and show short
  telomeres are tumor resistant, except when the
  p53 tumor suppressor protein is absent. (Blasco
  2001)