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性甾体激素对Src依赖性信号通路的调控:治疗意义

Src-dependent signalling pathway regulation by sex-steroid hormones: therapeutic implications.

作者信息

Migliaccio Antimo, Castoria Gabriella, Auricchio Ferdinando

机构信息

Dipartimento di Patologia Generale della II Università di Napoli, Via L. De Crecchio 7, 80138 Naples, Italy.

出版信息

Int J Biochem Cell Biol. 2007;39(7-8):1343-8. doi: 10.1016/j.biocel.2006.12.009. Epub 2007 Jan 24.

Abstract

Sex-steroid hormones trigger association of their receptors with signalling effectors, and activate complex networks. These effectors include Src and p85alpha, the PI3-kinase (PI3K) regulatory subunit. Remarkably, various hormonal effects, such as DNA synthesis of mammary and prostate cancer cells, vasorelaxation and migration of different cell types are evoked by this activation. In addition, there are reports on a limited but increasing number of cells responding to hormones through signalling activation in the absence of receptor-dependent transcriptional activity. Altogether these findings indicate that further study is required on signalling inhibitors to control progression of tumors expressing steroid receptors. In addition, new molecules interfering in recruitment of signalling effectors by steroid receptors and leaving unaffected the receptor transcriptional activity could be employed to reduce cell proliferation. Inhibitors of steroid receptor-dependent signal transduction might emerge as a new category of steroid receptor antagonists.

摘要

性类固醇激素促使其受体与信号效应器结合,并激活复杂的网络。这些效应器包括Src和p85α,即PI3激酶(PI3K)的调节亚基。值得注意的是,这种激活会引发各种激素效应,如乳腺和前列腺癌细胞的DNA合成、不同细胞类型的血管舒张和迁移。此外,有报道称,在缺乏受体依赖性转录活性的情况下,通过信号激活对激素作出反应的细胞数量有限但在增加。这些发现总体表明,需要对信号抑制剂进行进一步研究,以控制表达类固醇受体的肿瘤的进展。此外,可以采用新的分子来干扰类固醇受体对信号效应器的招募,同时不影响受体的转录活性,从而减少细胞增殖。类固醇受体依赖性信号转导的抑制剂可能会成为一类新的类固醇受体拮抗剂。

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