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Updated: Aug 13, 2026

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The intracellular form of notch blocks transforming growth factor beta-mediated growth arrest in Mv1Lu epithelial

Prakash Rao1, Tom Kadesch

  • 1Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104-6145, USA.

Molecular and Cellular Biology
|August 29, 2003
PubMed

Insights

Notch signaling activation prevents cells from responding to growth-inhibiting signals like TGF-beta by blocking cell cycle inhibitors. This deregulation of c-Myc expression contributes to uncontrolled cell growth and cancer.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Notch signaling is crucial for cell fate determination during development.
  • Constitutive activation of Notch signaling is implicated in cancer development.
  • The precise mechanisms linking Notch signaling to cell growth regulation remain unclear.

Purpose of the Study:

  • To investigate the role of Notch signaling in cell cycle control.
  • To elucidate how Notch signaling influences cellular responses to growth inhibitory signals.
  • To identify novel links between Notch and cell cycle regulation.

Main Methods:

  • Utilized Mv1Lu epithelial cells expressing an oncogenic form of Notch (NICD).
  • Assessed cellular resistance to transforming growth factor beta (TGF-beta)-induced cell cycle inhibition.
  • Analyzed the expression levels of cell cycle inhibitors (p15INK4B) and oncogenes (c-Myc).

Main Results:

  • Cells expressing NICD exhibited resistance to TGF-beta's growth-inhibitory effects.
  • NICD expression blocked the induction of the Cdk inhibitor p15INK4B.
  • c-Myc expression remained elevated in NICD-expressing cells, even under low serum conditions, indicating Notch's indirect deregulation of c-Myc.

Conclusions:

  • Notch signaling indirectly deregulates c-Myc expression.
  • This deregulation of c-Myc renders cells resistant to growth-inhibitory signals.
  • The findings suggest a novel mechanism by which Notch signaling contributes to uncontrolled cell proliferation and cancer.

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