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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways

L Weng1, J Brown, C Eng

  • 1Clinical Cancer Genetics and Human Cancer Genetics Programs, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.

Human Molecular Genetics
|February 13, 2001
PubMed

Insights

Tumor suppressor PTEN triggers cell death and G(1) arrest in breast cancer cells. PTEN-induced apoptosis is mediated by the phosphoinositol-3-kinase/Akt pathway, independent of cell cycle arrest.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • PTEN (phosphatase and tensin homolog) is a critical tumor suppressor.
  • PTEN regulates cell growth, survival, and cell cycle progression.
  • Previous studies show PTEN overexpression in MCF-7 cells induces G(1) arrest and cell death, potentially via PI3K/Akt pathways.

Purpose of the Study:

  • To investigate the mechanisms underlying PTEN-mediated growth suppression in MCF-7 breast cancer cells.
  • To elucidate the role of phosphoinositol-3-kinase (PI3K)/Akt signaling in PTEN-induced cell death and cell cycle arrest.
  • To determine if PTEN-induced apoptotic cells originate from G(1)-arrested cells.

Main Methods:

  • Overexpression of PTEN in MCF-7 breast cancer cells.
  • Culture under low growth factor conditions.
  • Treatment with caspase 9-specific inhibitor (ZVAD).
  • Overexpression of dominant-negative Akt.
  • Analysis of cell death and cell cycle distribution.

Main Results:

  • Low growth factor levels enhance PTEN-mediated growth suppression and cell death.
  • PTEN-induced cell death is blocked by ZVAD, but cell cycle arrest is unaffected.
  • PTEN-mediated cell death involves the PI3K/Akt pathway, while cell cycle arrest is PI3K/Akt-dependent and -independent.

Conclusions:

  • PTEN-induced apoptosis in MCF-7 cells does not originate from G(1)-arrested cells.
  • The PI3K/Akt pathway mediates PTEN's effect on cell death.
  • PTEN influences cell cycle arrest through both PI3K/Akt-dependent and -independent mechanisms.

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