Clonal variants of a melanoma cell line sensitive to growth inhibition by dexamethasone.

Clonal variants of a melanoma cell line sensitive to growth inhibition by dexamethasone.
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对地塞米松生长抑制敏感的黑色素瘤细胞系的克隆变体。

DOI:
10.1016/0014-4827(82)90187-2
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发表时间:
1982
影响因子:
3.7
通讯作者:
Horn,D
Horn,D
中科院分区:
医学3区
文献类型:
--
作者:
Buzard,RL;Hutchens,TW;Hawkins,EF;Markland,FS;Horn,D

文献摘要

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我们分离并鉴定了RPMI3460叙利亚仓鼠黑色素瘤细胞系的两个克隆,它们对合成的糖皮质激素地塞米松表现出不同的反应。在10 NM地塞米松存在下,一个克隆(克隆6)表现出亲代RPMI3460细胞系中观察到的生长抑制、形态变化和最终细胞密度降低。相反,另一个克隆(克隆5)虽然表现出最终细胞密度的降低,但没有表现出生长抑制和形态变化。因此,在这些细胞中,地塞米松对生长和形态的影响可以与地塞米松对最终细胞密度的影响分开表达。这一观察结果表明,这两组反应是可以单独控制的,糖皮质激素可能通过不同或不同的生物学途径发挥作用。体外受体分析表明,克隆5细胞与克隆6细胞相比,不同的表型不能用克隆5细胞胞浆糖皮质激素受体的缺失或减少来解释。额外的受体特性表明,克隆5和克隆6细胞对地塞米松的不同反应并不反映受体以稳定激活形式存在的能力的变化。细胞外成分在生长介质中的积累或消耗的差异似乎也不是克隆5细胞相对于克隆6细胞的表型改变的原因。
We have isolated and characterized two clones of the RPMI 3460 Syrian hamster melanoma cell line which exhibit different responses to the synthetic glucocorticoid dexamethasone. In the presence of 10 nM dexamethasone, one clone (clone 6) exhibits the growth inhibition, morphological alterations, and reduction in final cell density observed in the parental RPMI 3460 cell line. In contrast, the other clone (clone 5), although exhibiting a reduction in final cell density, fails to exhibit the growth inhibition and morphological alterations. Thus, the effect of dexamethasone on growth and morphology can be expressed separately from the effect of dexamethasone on final cell density in these cells. This observation suggests that the two sets of responses can be controlled separately and that glucocorticoids may exert their influence through different or divergent biological pathways.In vitro receptor assays suggest that the different phenotypes of clone 5 compared with clone 6 cells cannot be explained by an absence of or reduction in cytosolic glucocorticoid receptor, in clone 5 cells. Additional receptor characterization suggests that the different responses to dexamethasone of clone 5 and clone 6 cells do not reflect changes in the ability of receptor to exist in a stably activated form. Differences in the accumulation or depletion of extracellular components in the growth medium also do not seem to be responsible for the altered phenotype of clone 5 vis-à-vis clone 6 cells.