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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Oncogenic transformation of cells by a conditionally active form of the protein kinase Akt/PKB

A M Mirza1, A D Kohn, R A Roth

  • 1Cancer Research Institute, University of California, San Francisco/Mt. Zion Cancer Center, 94115, USA.

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|July 26, 2000
PubMed

Insights

A conditionally active form of Akt (Akt:ER*) promotes cell cycle progression and suppresses apoptosis in Rat1 cells. This Akt activation influences oncogenic transformation by altering cell morphology and promoting anchorage-independent growth.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • The Akt/PKB protein kinase plays a crucial role in regulating cell cycle progression and apoptosis.
  • Dysregulation of Akt signaling is frequently observed in cancer cells, contributing to oncogenic transformation.
  • Understanding Akt's precise functions in these processes is vital for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the role of a conditionally active form of Akt/PKB (M+ Akt:ER*) in oncogenic transformation.
  • To elucidate how Akt activation influences key cellular processes such as cell cycle progression, apoptosis, and cell morphology.
  • To explore the signaling pathways downstream of Akt activation, including MEK/ERK signaling.

Main Methods:

  • Utilized a conditionally active Akt/PKB construct (M+ Akt:ER*) in Rat1 cells.
  • Assessed changes in cell morphology, anchorage-independent growth, and apoptosis upon M+ Akt:ER* activation.
  • Monitored cell cycle progression (S and G2-M phases) and expression of cell cycle regulators (p27Kip1, CDK-2).
  • Investigated the activation of MAP/ERK Kinase (MEK) and ERK/MAP kinases and the effect of MEK inhibition.

Main Results:

  • Activation of M+ Akt:ER* induced morphological changes and efficient anchorage-independent growth in Rat1 cells.
  • M+ Akt:ER* activation suppressed apoptosis in detached Rat1 cells and promoted cell cycle progression from quiescence.
  • Decreased p27Kip1 expression and increased cyclin-dependent kinase-2 activity were observed following M+ Akt:ER* activation.
  • Akt activation led to rapid MEK/ERK activation, but MEK inhibition did not affect Akt-induced morphological changes.

Conclusions:

  • Conditionally active Akt (M+ Akt:ER*) is sufficient to induce significant alterations in cell morphology, growth, and survival.
  • Akt activation impacts cell cycle regulation by modulating p27Kip1 and CDK-2.
  • While Akt can activate MEK/ERK pathways, these may not be solely responsible for all observed Akt-mediated cellular changes.
  • The developed conditional transformation system provides a valuable tool for studying Akt's role in normal cellular responses and cancer proliferation.

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