Deregulation of tumor angiogenesis and blockade of tumor growth in PPARβ-deficient mice

Sabine Müller-Brüsselbach, Martin Kömhoff, Markus Rieck, Wolfgang Meissner, Kerstin Kaddatz, Jürgen Adamkiewicz, Boris Keil, Klaus J. Klose, Roland Moll, Andrew D. Burdick, Jeffrey M. Peters, Rolf Müller

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


The peroxisome proliferator-activated receptor-β (PPARβ) has been implicated in tumorigenesis, but its precise role remains unclear. Here, we show that the growth of syngeneic Pparb wild-type tumors is impaired in Pparb-/- mice, concomitant with a diminished blood flow and an abundance of hyperplastic microvascular structures. Matrigel plugs containing pro-angiogenic growth factors harbor increased numbers of morphologically immature, proliferating endothelial cells in Pparb-/- mice, and retroviral transduction of Pparb triggers microvessel maturation. We have identified the Cdkn1c gene encoding the cell cycle inhibitor p57Kip2 as a PPARβ target gene and a mediator of the PPARβ-mediated inhibition of cell proliferation, which provides a possible mechanistic explanation for the observed tumor endothelial hyperplasia and deregulation of tumor angiogenesis in Pparb-/- mice. Our data point to an unexpected essential role for PPARβ in constraining tumor endothelial cell proliferation to allow for the formation of functional tumor microvessels.

Original languageEnglish (US)
Pages (from-to)3686-3698
Number of pages13
JournalEMBO Journal
Issue number15
StatePublished - Aug 8 2007

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Molecular Biology
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


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