Suppression of tumorigenicity in Ras-transformed fibroblasts by alpha 2(I) collagen.
AffiliationCancer Research Campaign, Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
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AbstractTransformed fibroblasts exhibit reduced adhesion to substrata, a characteristic attributable in part to reduced expression/increased degradation of extracellular matrix (EM) proteins such as type I collagen. To directly assess the role of EM proteins in cellular transformation, a vKRas-transformed mouse fibroblast cell line was transfected with an alpha 2(I) collagen expression construct. Stable transfectants displaying a partial restoration of type I collagen expression showed a flatter morphology with increased adherence to the substratum. These clones also exhibited a reduced ability to clone in soft agar, slower growth kinetics, and suppression of tumorigenicity in nude mice. Restoration of type I collagen is correlated with down-regulation of ras oncogene-responsive NVL3 VL30 gene expression. These results suggest that in addition to suppressing tumorigenicity by promoting cellular adhesion and cytoskeletal organization, EM proteins such as type I collagen may also act to subvert oncoprotein signaling pathways associated with the malignant phenotype.
CitationSuppression of tumorigenicity in Ras-transformed fibroblasts by alpha 2(I) collagen. 1996, 7 (10):1353-60 Cell Growth Differ.
JournalCell Growth & Differentiation
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