Regulation of alpha 1 (I)-collagen gene expression in response to cell adhesion in Swiss 3T3 fibroblasts.
Nonadhesive conditions cause Swiss 3T3 fibroblasts to enter a quiescent state that is reversed upon reattachment to a surface. Previously, we demonstrated that adhesion in serum-free conditions is sufficient to activate suspension-arrested cells out of Go, with the induction of the growth-associated genes, c-fos, c-myc, and actin. In this study, we have employed this system to identify programs of gene expression that respond primarily to the adhesive state of the cell, rather than the growth state. We show that cells in different adhesive states can be distinguished by their patterns of protein synthesis. Analysis of one adhesion-responsive protein led to its identification as pro-alpha 1 (I)-collagen. Pro-alpha 1 (I)-collagen synthesis and mRNA levels are decreased up to 6-fold in suspension-arrested fibroblasts, but are enhanced up to 5-fold as cells approach confluence. This suggests that the reduced expression in suspension-arrested cells is not simply a result of quiescence. In addition, reattachment of suspended cells in serum-free conditions caused a 7-fold induction of collagen mRNA levels and a greater than 20-fold rise in the rate of procollagen synthesis. The expression of c-myc was induced during adhesion in serum-free medium as well as by serum addition to suspension-arrested cells. However, alpha 1 (I)-collagen gene expression was unaffected by serum in the absence of adhesion. These results indicate that collagen gene expression is directly responsive to cell adhesion, independent of the growth state.
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
J
J
Dhawan
S R
SR
Farmer
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D002460:Cell Line; D003094:Collagen / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics; D005786:Gene Expression Regulation; D007526:Isoelectric Point; D051379:Mice; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D011347:Procollagen / Q000235:genetics; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000378:metabolism; D015291:Transforming Growth Factors / Q000494:pharmacology
D005353:Fibronectins; D011347:Procollagen; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015291:Transforming Growth Factors; D003094:Collagen