Suppression of tumorigenicity in Ras-transformed fibroblasts by alpha 2(I) collagen.
Transformed 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.
Travers
H
H
Cancer Research Campaign, Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
French
N S
NS
Norton
J D
JD
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003094:Collagen / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D051379:Mice; D015398:Signal Transduction
D003094:Collagen