Objective: To investigate the expression of MtF, transferrin receptor 1 (TfR1) and ferritin (Fn) mRNAs in K562 leukemic cells during ATRA-induced cell differentiation and to explore the interrelationship between the expression levels of these iron metabolism-related molecules.
Methods: K562 cells cultured with or without ATRA (1 micromol/L) were collected at 24, 72 and 120 hours respectively. Cell differentiation toward granulocyte lineage was confirmed by microscopic study (Wright's staining) and flowcytometry. Expression levels of MtF, TfR1 and Fn were evaluated with semiquantitative RT-PCR, while K562 cells cultured without ATRA as control.
Results: Over 21.2% of K562 cells demonstrated features of granulocyte, and the expression of CD13 on cell surface increased significantly at day 5 with ATRA treatment (P < 0.05, compared with control). K562 cells could express a certain level of MtF before ATRA-induced differentiation. With increase of ATRA-induced cell differentiation, MtF mRNA expressions were downregulated progressively. After 5 days of induced cell differentiation, expression levels of MtF and TfR1 mRNA were just 86.5% and 79.2% of that before ATRA treatment. While Fn mRNA expression increased to 1.21 folds of that before ATRA treatment.
Conclusion: MtF expression is downregulated during ATRA-induced K562 cell differentiation, with concomitant downregulation of TfR1 and upregulation of Fn. The coordinated expression regulation of these key iron metabolism-related molecules during cell differentiation may in turn inhibit TfR1-mediated iron uptake via endocytosis and thus adversely affect cell proliferation potential.