Demethylation and expression of murine mammary tumor proviruses in mouse thymoma cell lines.
Demethylation and expression of murine mammary tumor proviruses in mouse thymoma cell lines.
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小鼠胸腺瘤细胞系中小鼠乳腺肿瘤原病毒的去甲基化和表达。
DOI：
10.1073/pnas.80.1.110
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发表时间：
1983
影响因子：
11.1
通讯作者：
Crépin,M
中科院分区：
文献类型：
--
作者：
Mermod,JJ;Bourgeois,S;Defer,N;Crépin,M
在对糖皮质激素的杀伤作用敏感的T淋巴细胞系（T1M1）和其两种变体（一种对糖皮质激素诱导的淋巴细胞溶解具有抗性（T1M1r）和一种对糖皮质激素诱导的淋巴细胞溶解超敏感（T1M1ss））中分析鼠乳腺肿瘤病毒（MMTV）的表达。在T1M1细胞系中，MMTV被表达并通过地塞米松短时间处理诱导约10倍。Southern印迹分析的限制性内切酶的DNA从T1M1细胞显示三个前病毒类似于正常C57 BL小鼠组织。在保留功能性糖皮质激素受体的T1M1ss系中，MMTV mRNA可被糖皮质激素诱导，而在糖皮质激素受体缺陷的T1M1r系中诱导减少。此外，T1M1r系在不存在激素的情况下表达显著升高的MMTV mRNA基础水平。在变异体中没有发生重排或重复感染，但在T1M1r变异体中所有含有5 '长末端重复序列的区域都被去甲基化，尽管前病毒的其他位点保持甲基化。由于这种变异是通过地塞米松长期治疗选择的，这些观察结果提高了这样的可能性，即在这种选择过程中发生的MMTV的连续转录可能导致糖皮质激素诱导的长末端重复序列的去甲基化。
Murine mammary tumor virus (MMTV) expression is analyzed in a T-lymphoid cell line (T1M1) sensitive to the killing effect of glucocorticoids and in two of its variants, one resistant (T1M1r) and one supersensitive (T1M1ss) to glucocorticoid-induced lymphocytolysis. In the T1M1 line, MMTV is expressed and induced approximately 10-fold by short treatment with dexamethasone. Southern blot analyses of restriction enzyme digests of DNA from T1M1 cells reveal three proviruses similar to those of normal C57BL mouse tissue. In the T1M1ss line, which has retained functional glucocorticoid receptors, MMTV mRNA is inducible by glucocorticoids, while induction is reduced in the T1M1r line defective in glucocorticoid receptors. Moreover, the T1M1r line expresses a strikingly elevated basal level of MMTV mRNA in the absence of hormone. No rearrangements or superinfection have occurred in the variants, but all the regions containing 5'-long terminal repeats are demethylated in the T1M1r variant although other sites of the provirus remain methylated. Because this variant was selected by prolonged treatment with dexamethasone, these observations raise the possibility that the continuous transcription of MMTV that occurred during this selection can result in glucocorticoid-induced demethylation of long-terminal-repeat sequences.