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.
Cancer Research Campaign, Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
H
H
Travers
N S
NS
French
J D
JD
Norton
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