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Related Experiment Videos

Immortal ALT+ human cells do not require telomerase reverse transcriptase for malignant transformation.

Beicheng Sun1, Meizhen Chen, Christina L Hawks

  • 1Department of Physiology and Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78245, USA.

Cancer Research
|August 3, 2005
PubMed
Summary

Alternative Lengthening of Telomeres (ALT) is sufficient for cancer cell immortalization and tumorigenesis. The study reveals ALT+ cells become fully tumorigenic with oncogenic RasV12G, challenging the necessity of telomerase reverse transcriptase (hTERT) in certain cancer models.

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Area of Science:

  • Oncology
  • Cell Biology
  • Genetics

Background:

  • Many human cancers maintain telomeres using the Alternative Lengthening of Telomeres (ALT) pathway instead of telomerase.
  • ALT-positive (ALT+) cancer cells are immortal but their tumorigenic potential can be context-dependent.
  • Previous studies suggested telomerase reverse transcriptase (hTERT) is crucial for tumor formation in ALT+ cells.

Purpose of the Study:

  • To investigate the role of oncogenic RasV12G and telomere maintenance mechanisms in the tumorigenicity of ALT+ human fibroblasts.
  • To compare the tumorigenic potential of ALT+ cells with and without hTERT expression.
  • To evaluate the impact of different implantation sites on the assessment of tumorigenicity.

Main Methods:

  • Transduction of ALT+ human SV40-immortalized fibroblasts with oncogenic RasV12G.

Related Experiment Videos

  • Tumorigenicity assays using subcutaneous (s.c.) injection and subrenal capsule implantation in immunodeficient mice.
  • Assessment of telomerase activity and telomere length maintenance.
  • Analysis of tumor invasion and metastasis.

    • Main Results:

    • RasV12G expression alone converted ALT+ fibroblasts into fully tumorigenic cells, capable of invasion and metastasis when implanted under the kidney capsule.
    • These RasV12G-expressing ALT+ cells remained telomerase-negative.
    • Introduction of hTERT did not significantly enhance the malignant properties of these cells.
    • When tested via s.c. injection, RasV12G-transduced ALT+ cells required hTERT for tumor formation, suggesting an artifact of the s.c. assay.

    Conclusions:

    • Alternative Lengthening of Telomeres (ALT) is a sufficient telomere maintenance mechanism for neoplastic transformation by oncogenes like RasV12G.
    • The subrenal capsule assay demonstrates that ALT is equivalent to hTERT in supporting oncogene-induced tumorigenesis.
    • The subcutaneous injection method may artifactually inflate the role of hTERT in tumorigenicity assays for ALT+ cells.