E1A 12S in the absence of E1B or other cooperating oncogenes enables cells to overcome apoptosis

M P Quinlan1

  • 1Department of Microbiology and Immunology, University of Tennessee, Memphis 38163.

Oncogene
|December 1, 1993
PubMed

Insights

The adenovirus E1A 12S gene prevents programmed cell death in neonatal rat kidney cells, promoting their continued proliferation and differentiation. This gene may act as an anti-apoptotic factor, preserving cell viability.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Neonatal rat kidneys undergo growth and differentiation post-birth.
  • Kidney epithelial cells in culture activate programmed cell death (apoptosis) within 24 hours.
  • Cellular proliferation ceases and cell death begins between 48-72 hours in culture.

Purpose of the Study:

  • To investigate the role of adenovirus E1A gene variants (12S and 13S) in regulating neonatal rat kidney cell proliferation and apoptosis.
  • To determine if E1A gene products can prevent or reverse programmed cell death in cultured kidney cells.
  • To assess the potential of E1A 12S as an anti-apoptotic gene.

Main Methods:

  • Culturing neonatal rat kidney epithelial cells.
  • Introducing adenovirus E1A 12S and/or E1B genes into the cells.
  • Analyzing DNA synthesis, proliferation, and cell death (apoptosis and necrosis) markers.
  • Evaluating the effect of E1A 12S on Madin Darby canine kidney (MDCK) cells under TGF-beta 1 inhibition.

Main Results:

  • Adenovirus E1A 12S gene restarts proliferation and maintains differentiation in cultured neonatal rat kidney cells, independent of serum.
  • E1A 12S prevents apoptosis, evidenced by the escape of cells retaining 12S sequences from programmed cell death.
  • Adenovirus E1A 13S gene expression induces necrosis, not apoptosis, and leads to cellular DNA degradation.
  • E1A 12S overcomes TGF-beta 1-induced inhibition of proliferation and apoptosis in MDCK cells.

Conclusions:

  • Adenovirus E1A 12S gene product acts as a potent stimulator of proliferation and differentiation in neonatal rat kidney cells.
  • E1A 12S demonstrates significant anti-apoptotic properties, protecting kidney epithelial cells from programmed cell death.
  • The E1A 13S gene variant induces necrosis, highlighting functional differences between E1A isoforms.
  • Adenovirus E1A 12S shows potential as a therapeutic agent to prevent kidney cell loss.

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