Prion protein modifies TGF-beta induced signal transduction.
Members of the transforming growth factor-beta (TGF-beta) superfamily regulate a multitude of cellular processes as well as the expression of various proteins such as, e.g., matrix metalloproteinases (MMPs). These endopeptidases selectively degrade components of the extracellular matrix as well as non-matrix substrates like growth factors and cell surface receptors. MMPs are activated during embryonic development, morphogenesis, and tissue resorption/remodeling as well as in pathological conditions such as deranged wound healing and cancer metastasis. In this report we demonstrate that over-expression of cellular prion protein in mouse mammary gland epithelial cells is able to modulate TGF-beta induced signal transduction leading to a synergistic increase of secreted MMP-2 activity. This correlates with elevated substrate detachment of cells grown as an epithelial monolayer as well as interfering with morphogenesis of cells cultured in a three-dimensional collagen type I matrix.
Wurm
Susanne
S
Upper Austrian Research GmbH, Center for Biomedical Nanotechnology, 4020 Linz, Austria.
Wechselberger
Christian
C
D000818:Animals; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008321:Mammary Glands, Animal / Q000166:cytology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011328:Prions / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D011328:Prions; D016212:Transforming Growth Factor beta; D003094:Collagen; D020782:Matrix Metalloproteinases