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Glucocorticoid receptors and cell cycle progression in human melanoma cell lines

✍ Scribed by A.-M. Osman; P. W. M. Jansen; L. A. Smets; C. Benckhuijsen


Publisher
John Wiley and Sons
Year
1985
Tongue
English
Weight
824 KB
Volume
125
Category
Article
ISSN
0021-9541

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✦ Synopsis


Proliferation of six established human melanoma cell lines was inhibited after treatment for 1 h with a high dose of glucocorticoid. Four of the lines with the capacity of colony formation were used to quantify final plating efficiency. Specific glucocorticoid binding sites in these cell lines ranged from 51,000 to 170,000 sites per cell as measured with a whole-cell assay. Growth inhibition was completely reversible in one cell line, irreversible in another, and partially reversible in two lines. Receptor content per cell correlated with the reduction in final plating efficiency of glucocorticoid-treated cells, suggesting a receptor-mediated event. A more than 90% growth inhibition and a 40% reduction in cell survival in the most sensitive cell line, M-5A, was accompanied by a dual blockage in G I and C21M phase that lasted till at least 96 h after treatment with 2.5 pM dexamethasone for 1 h. Evidence is presented of a real arrest of M-5A cells in G I phase and a markedly retarded progression through C2; the blockage of GI-S transition was immediate and complete. Accumulation of GI cells was observed in two other cell lines but was inconsistent in the fourth line studied by flow cytometry; in none of the three cell lines was G2/M accumulation observed. Stimulated melanogenesis after glucocorticoid treatment of M-5A and NKI-26 cells suggested differentiation of the cells during glucocorticoid-induced arrest.


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