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首页> 外文期刊>Molecular and Cellular Biology >Glucocorticoid receptor-dependent inhibition of cellular proliferation in dexamethasone-resistant and hypersensitive rat hepatoma cell variants.
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Glucocorticoid receptor-dependent inhibition of cellular proliferation in dexamethasone-resistant and hypersensitive rat hepatoma cell variants.

机译：糖皮质激素受体依赖性的地塞米松耐药和超敏大鼠肝癌细胞变异中细胞增殖的抑制作用。

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Exposure of the Fu5 rat hepatoma cell line to glucocorticoids, such as dexamethasone and hydrocortisone, suppressed the growth rate and final density of cells grown in the presence of serum. This hormonal effect was proportional to receptor occupancy and affinity and, in addition, the glucocorticoid antagonist RU38486 prevented this response. Two classes of dexamethasone-resistant variants that failed to be growth inhibited were recovered from ethyl methylsulfonate-mutagenized populations by continuous culture in the presence of 1 microM dexamethasone. The first class, represented by the EDR3 subclone, was completely glucocorticoid unresponsive and failed to express receptor transcripts. The second class, represented by the EDR1, EDR5, and EDR7 subclones, possessed significant levels of glucocorticoid receptor but were only partially glucocorticoid responsive when stimulated with saturating levels of hormone. Introduction of functional glucocorticoid receptor genes into both classes of dexamethasone-resistant variants by a recombinant retrovirus expression vector restored glucocorticoid responsiveness and suppression of cell growth. A hypersensitive variant (BDS1), recovered by bromodeoxyuridine selection, was fully glucocorticoid responsive, and its inhibition of proliferation was more acutely regulated by dexamethasone. Taken together, our results established that the inhibition of proliferation in Fu5 rat hepatoma cells represents a new glucocorticoid response that requires the expression of a functional glucocorticoid receptor.
机译：Fu5大鼠肝癌细胞系暴露于糖皮质激素（如地塞米松和氢化可的松）可抑制在血清存在下生长的细胞的生长速率和最终密度。这种激素作用与受体占有率和亲和力成正比，此外，糖皮质激素拮抗剂RU38486阻止了这种反应。通过在1 microM地塞米松的存在下连续培养，从甲基磺酸乙酯诱变的种群中回收了两类未能被抑制生长的地塞米松抗性变体。以EDR3亚克隆为代表的第一类完全是糖皮质激素无反应且不能表达受体转录物。以EDR1，EDR5和EDR7亚克隆为代表的第二类具有显着水平的糖皮质激素受体，但在饱和水平的激素刺激下仅部分糖皮质激素响应。通过重组逆转录病毒表达载体将功能性糖皮质激素受体基因引入两类地塞米松抗性变体中，恢复了糖皮质激素的响应性并抑制了细胞的生长。通过溴脱氧尿嘧啶核苷的选择而恢复的超敏变体（BDS1）具有完全的糖皮质激素反应性，地塞米松可以更严格地调节其对增殖的抑制作用。综上所述，我们的研究结果确定，Fu5大鼠肝癌细胞中增殖的抑制代表了一种新的糖皮质激素反应，需要表达功能性糖皮质激素受体。

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