c-myc expression is down-regulated by cell-cell and cell-extracellular matrix contacts in normal hepatocytes, but not in hepatoma cells.
Primary culture of adult rat hepatocytes resulted in marked increase of c-myc expression within a few hours. The high level of c-myc mRNA was maintained throughout culture on collagen-coated dishes, but decreased greatly with time during culture on collagen-gel or matrigel. Expression of c-myc was also down-regulated at high cell density. The decrease in its expression appeared closely related to inhibitions of DNA synthesis and cell spreading. In contrast, hepatoma H4TG cells showed a high level of c-myc expression which was not affected by culture on any extracellular matrices examined or by the cell density. These results suggest that up-regulation of expression of the c-myc gene is linked to G0 to G1 transition during cell cycle progression, which in normal hepatocytes is strictly regulated by cell-cell and cell-extracellular matrix interactions, but that this control mechanism is defective in malignant hepatic tumor cells.
Shimbara
N
N
Biomaterial Research Institute, Yokohama, Japan.
Takashina
M
M
Sato
C
C
Iizuka
M
M
Kobayashi
S
S
Tanaka
K
K
Ichihara
A
A
D000818:Animals; D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication; D005109:Extracellular Matrix / Q000502:physiology*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D007700:Kinetics; D008099:Liver / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D008297:Male; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains
D012313:RNA