Effect of estrogen sulfation by SULT1E1 and PAPSS on the development of estrogen-dependent cancers
Effect of estrogen sulfation by SULT1E1 and PAPSS on the development of estrogen-dependent cancers
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SULT1E1 和 PAPSS 硫酸化雌激素对雌激素依赖性癌症发展的影响
DOI：
10.1111/j.1349-7006.2012.02258.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.7
通讯作者：
Li, Xiaobo
中科院分区：
文献类型：
--
作者：
Xu, Yali;Liu, Xiaoxia;Li, Xiaobo
雌激素参与激素敏感肿瘤（包括乳腺癌和子宫内膜癌）的细胞增殖和凋亡的复杂调节。硫酸化是雌激素代谢的主要途径，被认为参与靶组织中雌激素的失活。 SULT1E1 和 PAPSS（PAPSS1 和 PAPSS2）通过提供催化酶和通用硫酸盐供体来负责雌激素硫酸化。本研究通过组织芯片分析和临床样本评估显示了乳腺和子宫内膜组织中SULT1E1和PAPSS的表达模式。肿瘤组织中的雌激素硫酸化酶比邻近的正常组织相对较高。 SULT1E1过表达抑制皮下异种移植模型中的肿瘤发生。通过CCK-8检测和流式细胞术检测，腺病毒过表达SULT1E1和PAPSS1可阻断MCF-7细胞中雌激素促增殖作用并促进H2O2诱导的细胞凋亡。通过实时逆转录聚合酶链反应和蛋白质印迹分析，SULT1E1和PAPSS1的过表达通过下调c-myc、cyclin D1和bcl-2的水平同时上调bax表达来抑制细胞生长并引发细胞凋亡。总之,SULT1E1和PAPSS在乳腺和子宫内膜肿瘤组织及其邻近正常组织中的表达差异显着。 SULT1E1 和 PAPSS1 的过度表达通过阻滞细胞周期和诱导细胞凋亡来延迟 MCF-7 细胞在体内和体外的生长。因此，靶向 SULT1E1 和 PAPSS 表达可能是治疗雌激素依赖性癌症的重要方法。 （癌症科学2012；103：10001009）
Estrogens are involved in the complex regulation of cell proliferation and apoptosis of hormone sensitive tumors including breast and endometrial cancers. Sulfation is the main pathway for estrogen metabolism, which is believed to be involved in the inactivation of estrogens in target tissues. SULT1E1 and PAPSS (PAPSS1 and PAPSS2) are responsible for the estrogen sulfation by providing catalyzing enzyme and universal sulfate donor. The present study showed the expression patterns of SULT1E1 and PAPSS in the breast and endometrial tissues by tissue array analysis and the assessment of clinical samples. The estrogen sulfation enzymes were comparatively higher in the tumorous tissues than their adjacent normal tissues. SULT1E1 overexpression inhibited the tumorigenesis in subcutaneous xenograft model. By CCK-8 assay and flow cytometry assay, overexpression of SULT1E1 and PAPSS1 by adenovirus blocked the estrogen pro-proliferating effect and promoted cell apoptosis induced by H2O2 in MCF-7 cells. By real-time reverse transcription-polymerase chain reaction and western-blot assays, overexpression of SULT1E1 and PAPSS1 suppressed cell growth and triggered apoptosis by downregulating the levels of c-myc, cyclin D1 and bcl-2, meanwhile, upregulating bax expression. In conclusion, the discrepancies in expressions of SULT1E1 and PAPSS between breast and endometrial tumorous tissues and their adjacent normal tissues were prominent. Overexpression of SULT1E1 and PAPSS1 retarded MCF-7 cells growth in vivo and in vitro by arresting cell cycles and inducing apoptosis. Thus, targeting SULT1E1 and PAPSS expressions might be an important approach for estrogen-dependent cancers. (Cancer Sci 2012; 103: 10001009)