Nair Binoj Chandrasekharan, Vadlamudi Ratna K
Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
Gene Ther Mol Biol. 2008 Jan 1;12:395.
Estrogen Receptor (ER) plays a central role in the development and progression of breast cancer. Hormonal therapy substantially improves disease-free survival of ER+ve breast tumors, however acquired resistance to endocrine therapies frequently occur. Emerging data implicate growth factor signaling pathways and their cross talk with ER as major cause of resistance. Both these pathways have been recently shown to use cell cycle machinery as downstream effectors in mediating therapy resistance. Several studies have demonstrated deregulation of cell cycle regulators and their cross talk with ER in therapy resistant tumors. The objective of this article is to review the underlying mechanisms by which tumor cells use cell cycle machinery to override hormonal therapy and to explore cell cycle machinery components as novel therapy targets for overcoming hormonal therapy resistance.
雌激素受体（ER）在乳腺癌的发生和发展中起着核心作用。激素疗法显著提高了ER阳性乳腺肿瘤的无病生存率，然而，对内分泌疗法的获得性耐药经常发生。新出现的数据表明，生长因子信号通路及其与ER的相互作用是耐药的主要原因。最近的研究表明，这两条通路均利用细胞周期机制作为下游效应器来介导治疗耐药性。多项研究已证明，在治疗耐药性肿瘤中，细胞周期调节因子失调及其与ER的相互作用。本文的目的是综述肿瘤细胞利用细胞周期机制克服激素疗法的潜在机制，并探索将细胞周期机制成分作为克服激素疗法耐药性的新型治疗靶点。
