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      Endothelin-1 and adrenomedullin enhance the growth of human adrenocortical carcinoma-derived SW-13 cell line by stimulating proliferation and inhibiting apoptosis.

      International Journal of Molecular Medicine

      pharmacology, Adrenocortical Carcinoma, genetics, pathology, Adrenocorticotropic Hormone, Adrenomedullin, Apoptosis, drug effects, Cell Line, Tumor, Cell Proliferation, DNA, Complementary, Endothelin-1, Humans, Microscopy, Electron, Transmission, Peptides

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          The human adrenocortical carcinoma-derived SW-13 cell line is currently used to study the interrelationships occurring between cytokines and growth factors and endothelins (ET) and adrenomedullin (AM). SW-13 cells express either ET-1 and AM or growth factors, and several cytokines stimulate ET-1 and AM release from SW-13 cells. However, neither the morphology and steroid-hormone secretion of SW-13 cells nor the expression of ET and AM receptors and the effects of ET and AM on SW-13 cell growth have been investigated. Electron microscopy showed that SW-13 cells were deprived of the typical organelles involved in steroid-hormone synthesis (i.e. mitochondrial with tubular cristae, smooth endoplasmic reticulum and lipid droplets), their prominent ultrastructural features being rough endoplasmic reticulum cisternae, free ribosomes and mitochondria with laminar cristae. Accordingly, steroid-hormone secretion was very low: no cortisol was produced and only very small amounts of aldosterone and its precursors were released. No appreciable secretory response to physiological concentrations of ACTH was observed. Reverse transcription-polymerase chain reaction showed the expression of pro ET-1 and proAM genes, as well as detected the mRNAs of only the ET- and AM-receptor subtypes, which are currently thought to mediate the growth-promoting action of these peptides: i.e. the ETA and AM2 receptors. In keeping with these observations, both ET-1 and AM markedly stimulated the growth of SW-13 cells, by enhancing the proliferation and lowering the apoptosis rate. Taken together, our findings allow us to conclude that SW-13 cannot be used for investigating the mechanisms involved in the regulation of steroid-hormone secretion, but are a suitable and useful model to study the role of endogenous ET and AM systems in the autocrine-paracrine control of human adrenocortical-cell growth.

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