Mechanism of transcriptional regulation by nuclear receptors

大多数前列腺癌和乳腺癌依赖于性类固醇激素在肿瘤发生中的作用。性类固醇激素的作用被认为是通过其核受体的转录调控介导的。对于核受体的激素依赖性调节，已经确定了许多不同的核复合物，包括染色质重塑和组蛋白修饰复合物。为了了解激素诱导的生殖器官癌症的发展，我们试图确定几种支持性类固醇激素受体的复合物。其中一个受体相互作用的复合体是剪接体复合体，该复合体在物理和功能上与人类雌激素受体a相关联。由于这种相互作用依赖于MAP激酶对内质网的磷酸化，我们提出乳腺癌发展中雌激素和生长因子信号的串扰介导RNA剪接控制。

The most of prostate and breast cancers are dependent on the actions of sex steroid hormones in tumorigenesis. The actions of sex steroid hormones are believed to be mediated through transcriptional regulations by their nuclear receptors. For hormone-dependent regulations by nuclear receptors, a number of different nuclear complexes have been identified, that include chromatin remodeling and histone modifying complexes. To understand the hormone-induced development of such reproductive organ cancers, we have tried to identify several complexes supporting the sex steroid hormone receptors. One of the receptor-interacting complexes has turned out a spliceosome complex, and this complex physically and functionally associate with the human estrogen receptor a. As this interaction was depending on the phospholiation of the ER by MAP kinase, we propose that cross-talk of estrogen and growth factor signalings in breast cancer development mediates RNA splicing control.