Journal Article

Akt mediates an angiogenic switch in transformed keratinocytes

Carmen Segrelles, Sergio Ruiz, Mirentxu Santos, Jesús Martínez-Palacio, M. Fernanda Lara and Jesús M. Paramio

in Carcinogenesis

Volume 25, issue 7, pages 1137-1147
Published in print July 2004 | ISSN: 0143-3334
Published online July 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh132
Akt mediates an angiogenic switch in transformed keratinocytes

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Akt signaling is involved in tumorigenesis via a number of different mechanisms that result in increased proliferation and decreased apoptosis. Previous data have demonstrated that Akt-mediated signaling is functionally involved in keratinocyte transformation. This work investigates the involvement of angiogenesis as a mediator of tumorigenesis in Akt-transformed keratinocytes. Tumors produced by subcutaneous injection of the latter showed increased angiogenic profiles associated with increased vascular endothelial growth factor (VEGF) protein levels. However, in contrast to v-rasHa-transformed keratinocytes, VEGF mRNA levels were not increased. The induction of VEGF protein by Akt is associated with increased phosphorylation and thus activation of p70S6K and eIF4E-binding protein 1, leading to increased VEGF translation. In addition, we observed increased metaloproteinases 2 and 9 expression, but not thrombospondin 1, in tumors derived from Akt-transformed keratinocytes. Collectively, these results demonstrate that Akt is an important mediator of angiogenesis in malignant keratinocytes through a post-transcriptional mechanism.

Keywords: HIF1α, hypoxia-inducible factor 1; MMP2, metaloproteinase 2; MMP9, metaloproteinase 9; TSP1, thrombospondin 1; TSP2 thrombospondin 2; VEGF, vascular endothelial growth factor

Journal Article.  6905 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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