Diversity of metallothionein content and subcellular localization in the National Cancer Institute tumor panel

Cancer Chemotherapy and Pharmacology
E S WooJ S Lazo

Abstract

Metallothioneins (MTs) are major thiol-containing intracellular proteins that bind metals, are induced by stress, and have been implicated in resistance to drugs and heavy metals. To examine the hypothesis that the protective functionality of MT may be dictated by its subcellular localization. We analyzed the basal MT content in 53 adherent cell lines of the National Cancer Institute (NCI) tumor panel and quantified the nuclear/cytoplasmic distribution of MT using confocal laser scanning microscopy and a recently described immunofluorescence-based algorithm. Among these cell types we found a 400-fold range in the basal MT levels and a tenfold range in the ratio of the nuclear to cytoplasmic MT immunostaining that was independent of basal MT content. Total MT levels and nuclear/cytoplasmic distribution were independent of total glutathione content, suggesting autonomous regulation of these protective protein and nonprotein thiol pools. Approximately 50% (29/53) of the cell lines had a greater nuclear than cytoplasmic MT density and were defined as having a karyophilic phenotype. Tissue specificity of MT localization was seen with breast cancer cell lines, which were cytoplasmophilic, whereas prostate-derived cells were karyophil...Continue Reading

Citations

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