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Inhibition of vascular smooth muscle cell proliferation, migration, and survival by the tumor suppressor protein PTEN.

Publication ,  Journal Article
Huang, J; Kontos, CD
Published in: Arterioscler Thromb Vasc Biol
May 1, 2002

Phosphatidylinositol (PI) 3-kinase signaling regulates numerous cellular processes, including proliferation, migration, and survival, which are required for neointimal hyperplasia and restenosis. The effectors of PI 3-kinase are activated by the phospholipid products of PI 3-kinase. In this report, we investigated the hypothesis that overexpression of the tumor suppressor protein PTEN, an inositol phosphatase specific for the products of PI 3-kinase, would inhibit the vascular smooth muscle cell (VSMC) responses necessary for neointimal hyperplasia and restenosis. Effects of PTEN were assessed in primary rabbit VSMCs after overexpression with a recombinant adenovirus and compared with uninfected or control virus-infected cells. PTEN was expressed endogenously in VSMCs, and PTEN overexpression inhibited PDGF-induced phosphorylation of p70(s6k), Akt, and glycogen synthase kinase-3-alpha and -beta but not ERK1 or -2. Overexpression of PTEN significantly inhibited both basal and PDGF-mediated VSMC proliferation and migration, the latter possibly due in part to downregulation of focal adhesion kinase. Moreover, PTEN overexpression induced cleavage of caspase-3 and significantly increased apoptosis compared with control cells. Taken together, these results demonstrate that PTEN overexpression potently inhibits the VSMC responses required for neointimal hyperplasia and restenosis. Adenovirus-expressed PTEN may therefore provide a useful tool for the local treatment of these and other vascular proliferative disorders.

Duke Scholars

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

May 1, 2002

Volume

22

Issue

5

Start / End Page

745 / 751

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Signal Transduction
  • Ribosomal Protein S6 Kinases
  • Rabbits
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huang, J., & Kontos, C. D. (2002). Inhibition of vascular smooth muscle cell proliferation, migration, and survival by the tumor suppressor protein PTEN. Arterioscler Thromb Vasc Biol, 22(5), 745–751. https://doi.org/10.1161/01.atv.0000016358.05294.8d
Huang, Jianhua, and Christopher D. Kontos. “Inhibition of vascular smooth muscle cell proliferation, migration, and survival by the tumor suppressor protein PTEN.Arterioscler Thromb Vasc Biol 22, no. 5 (May 1, 2002): 745–51. https://doi.org/10.1161/01.atv.0000016358.05294.8d.
Huang, Jianhua, and Christopher D. Kontos. “Inhibition of vascular smooth muscle cell proliferation, migration, and survival by the tumor suppressor protein PTEN.Arterioscler Thromb Vasc Biol, vol. 22, no. 5, May 2002, pp. 745–51. Pubmed, doi:10.1161/01.atv.0000016358.05294.8d.
Huang J, Kontos CD. Inhibition of vascular smooth muscle cell proliferation, migration, and survival by the tumor suppressor protein PTEN. Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):745–751.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

May 1, 2002

Volume

22

Issue

5

Start / End Page

745 / 751

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Signal Transduction
  • Ribosomal Protein S6 Kinases
  • Rabbits
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase