Journal Article

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

Liang-Ping Weng, Jessica L. Brown and Charis Eng

in Human Molecular Genetics

Volume 10, issue 3, pages 237-242
Published in print February 2001 | ISSN: 0964-6906
Published online February 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.3.237
PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and ‐independent pathways

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The tumour suppressor PTEN inhibits cell growth through multiple mechanisms. We have previously demonstrated that overexpression of PTEN in MCF-7 breast cancer cells causes G1 arrest followed by cell death, the latter of which is believed to be mediated by the phosphoinositol-3-kinase (PI3K) and Akt/PKB pro-apoptotic pathways. In this present study, we show that culture in the presence of low levels of growth factors increased PTEN-mediated growth suppression through the enhancement of PTEN-induced cell death. The caspase 9-specific inhibitor, ZVAD, blocked PTEN-induced cell death without altering the effect of PTEN on cell cycle distribution. Depending on the level of expression, overexpression of dominant-negative Akt induces more cell death and has less effect on the cell cycle or induces similar or decreased cell death without affecting the cell cycle compared with effects on cell death and the cell cycle when overexpressing PTEN. These observations in sum suggest that, in MCF-7 breast cancer cells, the apoptotic cells induced by the overexpression of PTEN did not derive from the G1-arrested cells. Further, the effect of PTEN on cell death is mediated through the PI3K/Akt pathway whereas PTEN-mediated cell cycle arrests are through PI3K/Akt-dependent and -independent pathways.

Journal Article.  5109 words.  Illustrated.

Subjects: Genetics and Genomics

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