Phosphoenolpyruvate carboxykinase is induced in growth-arrested hepatoma cells.
Phosphoenolpyruvate carboxykinase (PEPCK) mRNA is elevated in H4IIEC3 rat hepatoma cells cultured at high density, suggesting that PEPCK expression and growth arrest may be coordinately regulated. Induction of growth arrest either by contact inhibition (high culture density) or by serum deprivation correlated with significant increases in PEPCK protein and its mRNA. The observation that PEPCK mRNA was induced by contact inhibition in the presence of serum indicates that the effect of high density is independent of insulin or any other serum component. The magnitudes of the changes in PEPCK expression during growth arrest were greatly enhanced in KRC-7 cells, an H4IIEC3 subclone that is much more sensitive to growth arrest than its parental cell line. Restimulation of proliferation in growth-arrested KRC-7 cells, either by addition of serum or insulin to serum-deprived cells or by replating contact-inhibited cells at low density, caused a rapid decrease in PEPCK expression. However, PEPCK mRNA is not always reduced in proliferating cells since treatment of serum-starved cells with epidermal growth factor stimulated entry into the cell cycle but did not affect PEPCK mRNA levels. Finally, dexamethasone induction of PEPCK mRNA was blunted in cells cultured at high density but was unaffected by the presence or absence of serum. Collectively, these data suggest the possibility of cross-talk between the control of PEPCK expression and growth arrest in KRC-7 cells.
Zeitouni
Nawal
N
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Eubank
Darrell W
DW
Lee
Alex Q
AQ
Oxford
Misti G
MG
Freeman
Thomas L
TL
Mailliard
Mark E
ME
Beale
Elmus G
EG
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D002452:Cell Count; D002455:Cell Division / Q000235:genetics; D016895:Culture Media, Serum-Free; D004790:Enzyme Induction / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D007399:Interphase / Q000235:genetics; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016196:S Phase / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D010729:Phosphoenolpyruvate Carboxykinase (GTP)