Expression of liver X receptors in normal and refractory carcinoma tissues of the human lung and pancreas.
Expression of liver X receptors in normal and refractory carcinoma tissues of the human lung and pancreas.
复制标题
DOI：
10.14670/hh-11-949
复制
发表时间：
2018-05
影响因子：
2
通讯作者：
K. Kashiwagi;Mai Yanagida;Daiki Matsui;Mizuko Tanaka;K. Sugimoto;Honglei Chen;Naoki Ichikawa-Tomikawa;S. Marubashi;Hiroyuki Suzuki;H. Chiba
中科院分区：
文献类型：
--
作者：
K. Kashiwagi;Mai Yanagida;Daiki Matsui;Mizuko Tanaka;K. Sugimoto;Honglei Chen;Naoki Ichikawa-Tomikawa;S. Marubashi;Hiroyuki Suzuki;H. Chiba
肝X受体(LXRs)不仅参与维持胆固醇的稳态，而且在许多类型的正常和肿瘤细胞中也参与控制细胞生长。我们先前报道了LXRα在口腔鳞状细胞癌组织和细胞系中的异常表达，并且LXR刺激通过促进胆固醇外流导致口腔鳞癌细胞的增殖显著降低。由于LXR及其下游参与胆固醇代谢的蛋白也可作为小细胞肺癌(SCLC)和胰腺导管腺癌(PDAC)的治疗靶点，我们在此分析了LXR蛋白在这些难治性癌症以及正常人类肺和胰腺组织中的分布。LxRβ在纤毛上皮细胞、支气管腺上皮细胞、肺泡II型上皮细胞和肺泡巨噬细胞中有表达，在支气管基底细胞和I型肺泡上皮细胞中表达较少。此外，LXRβ在胰管上皮细胞和胰腺腺泡细胞中表达，在胰岛细胞中表达较弱。相反，LXRα的表达仅限于肺泡巨噬细胞，而在肺和胰腺的任何类型的上皮细胞中都不明显。9例小细胞肺癌和2 0例肺上皮癌组织中均有LXRβ的高表达，而LXRα无表达。这些发现为评估LXR靶向治疗小细胞肺癌和小细胞肺癌的疗效提供了基本信息。
Liver X receptors (LXRs) participate not only in maintaining cholesterol homeostasis but also in controlling cellular growth in many types of normal and tumor cells. We previously reported that LXRα was aberrantly expressed in human oral squamous cell carcinoma (HOSCC) tissues and cell lines, and that LXR stimulation led to significant reduction of proliferation of HOSCC cells via accelerating cholesterol efflux. Since LXRs and downstream proteins involved in cholesterol metabolism could be also applied as therapeutic targets in small cell lung carcinoma (SCLC) and pancreatic ductal adenocarcinoma (PDAC), we herein analyzed the distribution of LXR proteins in these refractory cancers as well as in normal human lung and pancreatic tissues. LXRβ was observed in ciliated epithelial cells, bronchial gland epithelia, type II alveolar epithelia and alveolar macrophages of the lung, and was less expressed in bronchial basal cells and type I alveolar epithelia. In addition, LXRβ was detected in epithelium of the pancreatic duct and acinar cells of the pancreas, and was weakly expressed in pancreatic islet cells. By contrast, LXRα expression was restricted to alveolar macrophages, and was not evident in any types of epithelial cells in the lung and pancreas. We also demonstrated that LXRβ but not LXRα was abundantly expressed in nine cases of SCLC and twenty cases of PDAC tissues. These findings provide basic information for evaluating the efficacy of LXR-targeted treatment in SCLC and PDAC.