Tsao M S, Sanders G H, Grisham J W
Exp Cell Res. 1987 Jul;171(1):52-62. doi: 10.1016/0014-4827(87)90250-3.
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.
一种非致瘤性且依赖贴壁生长的肝上皮细胞系（WB-F344）的传代后期细胞，其持续产生胰岛素样生长因子II和转化生长因子β，在仅添加转铁蛋白的无血清培养基中生长。在有转铁蛋白存在的情况下，表皮生长因子可进一步促进细胞群体生长，尽管单独的表皮生长因子无此作用。胰岛素、血小板衍生生长因子以及几种无机铁盐在没有转铁蛋白时也无法支持细胞生长；此外，这些因子不会增强转铁蛋白的作用。转铁蛋白促进细胞群体生长的作用在浓度为0.5 nM或更高时出现，在浓度约为6 nM时达到最大效果。一种亲脂性铁螯合剂，吡啶醛异烟酰腙铁（FePIH），可以完全模拟转铁蛋白对WB-F344细胞增殖的作用，但所需的摩尔浓度仅为转铁蛋白的。这些结果表明，转铁蛋白在WB-F344细胞增殖中的关键功能可能是将铁传递给细胞。在没有转铁蛋白的情况下，WB-F344细胞在无血清培养基中的增殖在G0/G1期停滞，在添加转铁蛋白后需要一段蛋白质合成期，细胞才能进入S期并启动DNA合成。更换转铁蛋白会使静止的WB-F344细胞同步化地进入细胞周期。表皮生长因子不会改变S期之前的潜伏期长度，但似乎会随后刺激[3H]胸腺嘧啶核苷的摄取。转铁蛋白可能作为一种“感受态”和/或“进展”因子，使这些上皮细胞能够在体外进行复制。
