TY - JOUR
T1 - De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells
AU - Santra, Manoranjan
AU - Skorski, Tomasz
AU - Calabretta, Bruno
AU - Lattime, Edmund C.
AU - Iozzo, Renato V.
PY - 1995/7/18
Y1 - 1995/7/18
N2 - The rapid progress in the cloning of proteoglycan genes has enabled investigators to examine in depth the functional roles these polyhedric molecules play in the control of cell proliferation. Decorin, a leucine-rich proteoglycan expressed by most connective tissues, is a prototype molecule that regulates cellular growth via two mechanisms: modulation of growth factor activity and matrix assembly. We now provide direct evidence that human colon cancer cells stably transfected with decorin cDNA exhibit a marked suppression of the transformed phenotype: the cells have a reduced growth rate in vitro, form small colonies in soft agar, and do not generate tumors in scid/scid mice. Several independent clones are arrested in the G1 phase of the cell cycle, and their growth suppression can be restored by treatment with decorin antisense oligodeoxynucleotides. These effects are independent of growth factors and are not due to either clonal selection or integration site of the decorin gene. These findings correlate well with the observation that decorin gene expression is markedly up-regulated during quiescence. Decorin thus appears to be one component of a negative loop that controls cell growth.
AB - The rapid progress in the cloning of proteoglycan genes has enabled investigators to examine in depth the functional roles these polyhedric molecules play in the control of cell proliferation. Decorin, a leucine-rich proteoglycan expressed by most connective tissues, is a prototype molecule that regulates cellular growth via two mechanisms: modulation of growth factor activity and matrix assembly. We now provide direct evidence that human colon cancer cells stably transfected with decorin cDNA exhibit a marked suppression of the transformed phenotype: the cells have a reduced growth rate in vitro, form small colonies in soft agar, and do not generate tumors in scid/scid mice. Several independent clones are arrested in the G1 phase of the cell cycle, and their growth suppression can be restored by treatment with decorin antisense oligodeoxynucleotides. These effects are independent of growth factors and are not due to either clonal selection or integration site of the decorin gene. These findings correlate well with the observation that decorin gene expression is markedly up-regulated during quiescence. Decorin thus appears to be one component of a negative loop that controls cell growth.
KW - Antisense Elements (Genetics)/pharmacology
KW - Carcinoma/genetics
KW - Cell Cycle/physiology
KW - Colonic Neoplasms/genetics
KW - Decorin
KW - Extracellular Matrix Proteins
KW - Gene Expression
KW - Genes, Tumor Suppressor/genetics
KW - Humans
KW - Neoplasms, Experimental
KW - Phenotype
KW - Proteoglycans/biosynthesis
KW - Transfection
UR - http://www.scopus.com/inward/record.url?scp=0029088680&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:A1995RJ89200073&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1073/pnas.92.15.7016
DO - 10.1073/pnas.92.15.7016
M3 - Article
C2 - 7624361
SN - 0027-8424
VL - 92
SP - 7016
EP - 7020
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -