title: [Expression of mitochondrial ferritin in K562 leukemic cell during TPA-induced cell differentiation].
abstract: Mitochondrial ferritin (MtF), a new player in iron metabolism, first identified in 2001, is highly homologous to ferritin both structurally and functionally. Preliminary studies have suggested that MtF might play very important roles in the regulation of mitochondrial iron homeostasis. Leukemic cells, just like other malignant cells, demand more iron for their greater proliferation potential. However, little is known about what roles MtF might play in leukemic cell iron metabolism and cell proliferation. The aim of this study was to investigate the expression of MtF, transferrin receptor 1 (TfR1) and ferritin (Fn) mRNAs in K562 leukemic cells during TPA-induced cell differentiation and to explore the interrelationship between the expression levels of these iron metabolism-related molecules. K562 cells cultured with or without TPA (16 nmol/L) were collected at 24, 72 and 120 hours respectively. Cell differentiation toward monocyte lineage was confirmed by microscopic study (Wright's staining) and flow cytometry. Semiquantitative RT-PCR was performed to determine mRNA expression, with house-keeping gene beta-actin as control reference. This study revealed that over 95% of K562 cells showed morphological features of monocyte/macrophage, and the expression of CD64 on cell surface increased significantly at day 5 with TPA treatment. K562 cells could express a certain level of MtF before TPA-induced differentiation. With increase of TPA-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 50.3% and 68.2% of that before TPA treatment. While Fn mRNA expression increased to 1.97 folds of that before TPA treatment. It is concluded that MtF expression is downregulated during TPA-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.
authors.affiliation: Department of Pediatric Hematology, West China Second Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
authors.forename: Li-Xing
authors.initials: LX
authors.lastname: Yuan
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Chen
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Pan
authors.forename: Chen-Yan
authors.initials: CY
authors.lastname: Zhou
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Zhu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005293:Ferritins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D035925:Iron-Regulatory Proteins / Q000378:metabolism; D020014:K562 Cells; D008928:Mitochondria / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011990:Receptors, Transferrin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D005293:Ferritins; D013755:Tetradecanoylphorbol Acetate