Regulation of growth of cultured hepatic epithelial cells by transferrin.
Late-passage cells of a nontumorigenic and anchorage-dependent hepatic epithelial line (WB-F344), which produce insulinlike growth factor II and transforming growth factor beta constitutively, grow in serum-free medium supplemented only with transferrin. In the presence of transferrin, epidermal growth factor further augments population growth, although epidermal growth factor alone is without effect. Insulin, platelet-derived growth factor, and several inorganic iron salts are also ineffective in supporting cell growth in the absence of transferrin; furthermore, these factors do not augment the action of transferrin. The population growth-promoting effect of transferrin occurs at concentrations of 0.5 nM or greater and the maximal effect is reached with a concentration of approximately 6 nM. A lipophilic iron chelator, ferric pyridoxal isonicotinoyl hydrazone (FePIH), can fully mimic the effect of transferrin on the proliferation of WB-F344 cells, but the molar concentration of transferrin. These results suggest that the critical function of transferrin in the proliferation of WB-F344 cells may be in the delivery of iron to the cells. In the absence of transferrin the proliferation of WB-F344 cells is arrested in serum-free medium in the G0/G1 phase, and a period of protein synthesis after the addition of transferrin is necessary before the cells can proceed to S phase and initiate DNA synthesis. Replacement of transferrin causes quiescent WB-F344 cells to cycle parasynchronously. Epidermal growth factor does not alter the length of the latency period prior to S phase but appears to stimulate the uptake of [3H]thymidine subsequently. Transferrin may act as a "competence" and/or "progression" factor, allowing the replication of these epithelial cell in vitro.
Tsao
M S
MS
Sanders
G H
GH
Grisham
J W
JW
D000818:Animals; D001769:Blood; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects; D007538:Isoniazid / Q000031:analogs & derivatives / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011730:Pyridoxal / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D014168:Transferrin / Q000494:pharmacology*
D002614:Chelating Agents; D003470:Culture Media; D007328:Insulin; D014168:Transferrin; D011730:Pyridoxal; D004815:Epidermal Growth Factor; C021079:pyridoxal isonicotinoyl hydrazone; D004247:DNA; D003513:Cycloheximide; D007538:Isoniazid