Abstract
Metallothionein (MT) was reported to be a potential negative regulator of apoptosis, and various reports have suggested that it may play roles in carcinogenesis and drug resistance, in at least a portion of cancer cells. The author summarizes the current understanding of the molecular functions of MT for tumor cell growth and drug resistance. These activities are regulated through intracellular metal ion modulation and free radical scavenging. Compared with analyses of solid tumors, few studies have analyzed the roles of MT in hematological malignancies. This review mainly describes the functions of MT in hematopoietic cells. Furthermore, through expression analyses of leukemias and lymphomas, the roles of MT in the biology of these diseases are particularly focused upon.
Highlights
Metallothionein (MT) was first isolated by Margoshes and Vallee [1] as a cadmium-binding low-molecular weight protein from the horse kidney
Since MT binds to metal ions, MTs may play a role in the hematopoietic cell proliferation/differentiation
In 24 acute myeloid leukemia (AML) cases, we previously reported that PU.1 expression was inversely correlated with the tyrosine kinase receptor FLT3 [74], and that strong expression of wild-type FLT3 was an unfavorable prognostic factor for overall survival [75,76]
Summary
Metallothionein (MT) was first isolated by Margoshes and Vallee [1] as a cadmium-binding low-molecular weight protein from the horse kidney. Structural studies have shown that these unusual proteins with 61 amino acids can bind to both essential metals (zinc and copper) and toxic metals (cadmium and mercury). MTs are characterized by their low molecular weight, high cysteine content, lack of aromatic amino acid residues and presence of 7–12 metal atoms per molecule [3,4]. Owing to their rich thiol content, MTs bind a number of trace metals including zinc, cadmium, mercury, platinum and silver, and protect cells and tissues against heavy metal toxicity. Since MT binds to metal ions, MTs may play a role in the hematopoietic cell proliferation/differentiation
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