甲磺酸地塞米松21-甲酯抗糖皮质激素作用机制：II. 受体-抗糖皮质激素复合物不能有效地与小鼠乳腺肿瘤病毒长末端重复序列染色质相互作用。

Mechanism of dexamethasone 21-mesylate antiglucocorticoid action: II. Receptor-antiglucocorticoid complexes do not interact productively with mouse mammary tumor virus long terminal repeat chromatin.

作者信息

Richard-Foy H, Sistare F D, Riegel A T, Simons S S, Hager G L

机构信息

Hormone Action and Oncogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

出版信息

Mol Endocrinol. 1987 Sep;1(9):659-65. doi: 10.1210/mend-1-9-659.

DOI:10.1210/mend-1-9-659

PMID:2856414

Abstract

We have studied the interaction of covalent dexamethasone 21-mesylate (DM) labeled, activated glucocorticoid receptor with mouse mammary tumor virus (MMTV) chromatin. Studies were performed on a murine cell line (904.13) which contains 200 copies per cell of a MMTV long terminal repeat (LTR) v-rasH casette mobilized on bovine papilloma virus based episomes. DM binds covalently to glucocorticoid receptors and displays almost full antagonist activity in this cell line. In situ transcription extension assays indicate that activated receptor-DM complex cannot stimulate LTR-initiated transcription. The receptor-DM complex also fails to induce DNase I hypersensitivity (HSR) and transcription factor loading at the MMTV promoter. Transcription activation, HSR formation, and factor binding induced with the agonist dexamethasone are blocked by covalent occupation of the receptor by DM. Although DM-activated receptor binds specifically to receptor sites on purified LTR DNA, the antagonist receptor complex does not interact productively with MMTV LTR chromatin in vivo.

摘要

我们研究了共价标记的甲磺酸地塞米松21酯（DM）激活的糖皮质激素受体与小鼠乳腺肿瘤病毒（MMTV）染色质之间的相互作用。研究是在一种鼠细胞系（904.13）上进行的，该细胞系每个细胞含有200个拷贝的MMTV长末端重复序列（LTR）v-rasH盒，其基于牛乳头瘤病毒的附加体进行动员。DM与糖皮质激素受体共价结合，并在该细胞系中表现出几乎完全的拮抗活性。原位转录延伸分析表明，激活的受体-DM复合物不能刺激LTR启动的转录。受体-DM复合物也不能诱导MMTV启动子处的DNase I超敏反应（HSR）和转录因子加载。激动剂地塞米松诱导的转录激活、HSR形成和因子结合被DM对受体的共价占据所阻断。尽管DM激活的受体能特异性结合纯化的LTR DNA上的受体位点，但拮抗剂受体复合物在体内不能与MMTV LTR染色质发生有效相互作用。