Regulation of SVEP1 gene expression by 17β-estradiol and TNFα in pre-osteoblastic and mammary adenocarcinoma cells
Regulation of SVEP1 gene expression by 17β-estradiol and TNFα in pre-osteoblastic and mammary adenocarcinoma cells
复制标题
DOI：
10.1016/j.jsbmb.2011.12.015
复制
发表时间：
2012-05-01
影响因子：
4.1
通讯作者：
Benayahu, D.
中科院分区：
文献类型：
--
作者：
Glait-Santar, C.;Benayahu, D.
乳腺癌是包括前列腺、甲状腺和肾脏在内的几种肿瘤之一，这些肿瘤显示出明显的骨转移倾向。肿瘤细胞对骨转移的偏好依赖于肿瘤细胞、骨髓微环境和骨细胞之间的特异性相互作用。骨仿生被认为能够使骨组织中的肿瘤细胞存活。利用基因芯片和RT-PCR技术，我们证实了少数骨基质蛋白以及细胞黏附分子在乳腺癌细胞中的信息表达。一种名为SVEP1的CAM分子此前已被证明在体内和体外成骨细胞中表达，介导细胞在骨髓壁龛中的黏附。雌二醇(17βE-2)和TINIFα都调节黏附分子的表达，并在骨癌串扰中发挥作用。我们比较了成骨前细胞MBA-15和乳腺腺癌细胞DA3对SVEP1基因的差异调控。17βE-2和肿瘤坏死因子α激活SVEP1启动子，增加其在两种细胞中的信息和蛋白水平。采用染色质免疫沉淀法，我们定量了转录因子对SVEP1启动子的占有率：TFIIB、ERα、NF-kappa B、Sp1，它们的结合也受到这两种因子的调节。通过对成骨前细胞和乳腺腺癌细胞的比较，本研究加深了我们对SVEP1基因表达调控的理解，并为其参与骨-癌-微环境的相互作用提供了线索。官方版权所有(C)201 1由爱思唯尔有限公司出版。保留所有权利。
Breast cancer is one of several tumors, including prostate, thyroid and kidney, which display a remarkable predilection for metastasis to bone. The preference to metastasize to bone by tumor cells relies on specific interactions among tumor cells, bone marrow microenvironment and bone cells. Osteomimicry is postulated to enable the survival of tumor cells in the bone tissue. Using gene profiling array and RT-PCR we demonstrated the message expression of few bone matrix proteins in mammary adenocarcinoma cells as well as that of cell adhesion molecules (CAMs). A CAM molecule, named SVEP1, was previously shown to be expressed in osteoblastic cells both in vivo and in vitro mediating cell adhesion in the bone-marrow niches. Both estradiol (17 beta E-2) and TINIF alpha regulate the expression of adhesion molecules and act in bone-cancer-crosstalk. We focused on differential regulation of SVEP1 gene comparing pre-osteoblastic MBA-15 and mammary adenocarcinoma DA3 cells. 17 beta E-2 and TNF alpha activated SVEP1 promoter, increased its message and protein levels in both cell types. Using chromatin immunoprecipitation assay, we quantified SVEP1 promoter occupancy by transcription factors; TFIIB, ER alpha, NF-kappa B, Sp1 and their binding was also regulated by both factors. By comparing pre-osteoblastic with mammary adenocarcinoma cells, the study expands our understanding of SVEP1 gene expression regulation and it sheds light on its involvement in bone-cancer-microenvironment interactions. Crown Copyright (C) 201 1 Published by Elsevier Ltd. All rights reserved.