We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Deregulation of tumor angiogenesis and blockade of tumor growth in PPARβ-deficient mice.
- Authors
Müller-Brüsselbach, Sabine; Kömhoff, Martin; Rieck, Markus; Meissner, Wolfgang; Kaddatz, Kerstin; Adamkiewicz, Jürgen; Keil, Boris; Klose, Klaus J.; Moll, Roland; Burdick, Andrew D.; Peters, Jeffrey M.; Müller, Rolf
- Abstract
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.
- Subjects
PEROXISOMES; NUCLEAR receptors (Biochemistry); TUMOR growth; NEOVASCULARIZATION; BLOOD-vessel development; CELLULAR pathology; HYPERPLASIA
- Publication
EMBO Journal, 2007, Vol 26, Issue 15, p3686
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601803