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Regulation of growth of cultured hepatic epithelial cells by transferrin

, : Regulation of growth of cultured hepatic epithelial cells by transferrin. Experimental Cell Research 171(1): 52-62

Late-passage cells of a nontumorigenic and anchorage-dependent hepatic epithelial line (WB-F344), which produce insulin-like 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 f 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 FePIH required to promote cell proliferation is 1000-fold higher than 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 Go/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 "complete" and/or "progression" factor, allowing the replication of these epithelial cells in vitro.

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Accession: 006288305

PMID: 3305046

DOI: 10.1016/0014-4827(87)90250-3

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