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Thymidylate synthase as an oncogene: a novel role for an essential DNA synthesis enzyme

Lambratu Rahman1, Donna Voeller, Monzur Rahman

  • 1Basic Research Laboratory and Molecular Therapeutic Program, National Institute of Health, Bethesda, MD 20892, USA.

Cancer Cell
|April 20, 2004
PubMed

Insights

Thymidylate synthase (TS) acts as an oncogene, driving cancer development. Overexpressing active TS transforms cells and causes tumors, while inactive mutants do not, highlighting TS

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Enzymology

Background:

  • Thymidylate synthase (TS) is crucial for DNA synthesis and repair.
  • Elevated TS levels in cancers correlate with poor patient prognosis across multiple cancer types.
  • TS is regulated by E2F1, a key cell cycle transcription factor.

Purpose of the Study:

  • To investigate the oncogenic potential of thymidylate synthase (TS).
  • To determine if catalytically active TS can induce a transformed phenotype in mammalian cells.
  • To explore the consequences of TS overexpression on cell viability.

Main Methods:

  • Ectopic expression of catalytically active TS and its mutants in mammalian cells.
  • Assays for transformed cell characteristics: foci formation, anchorage-independent growth, and tumor formation in nude mice.
  • Assessment of apoptosis following serum deprivation in TS-overexpressing cells.

Main Results:

  • Ectopic expression of active TS induced foci formation, anchorage-independent growth, and tumor formation in vivo.
  • TS mutants with impaired catalytic activity failed to induce these transforming effects.
  • Overexpression of TS led to apoptotic cell death upon serum removal.

Conclusions:

  • Catalytically active thymidylate synthase exhibits oncogene-like properties.
  • TS overexpression can drive neoplastic transformation and tumor development.
  • A link exists between TS-mediated DNA synthesis regulation and the induction of a neoplastic phenotype.

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