State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center, Nanjing University, Nanjing 210093, China.
J Biol Chem. 2012 Nov 23;287(48):40140-9. doi: 10.1074/jbc.M112.348763. Epub 2012 Aug 20.
Hepatocarcinoma cancer (HCC) occurs more often in men than in women, and little is known about its underlying molecular mechanisms.
We identify that 17β-estradiol (E2) could suppress tumor growth via regulating the polarization of macrophages.
Estrogen functions as a suppressor for macrophage alternative activation.
These studies introduce a novel mechanism for suppressing male-predominant HCC. Hepatocarcinoma cancer (HCC), one of the most malignant cancers, occurs significantly more often in men than in women; however, little is known about its underlying molecular mechanisms. Here we identified that 17β-estradiol (E2) could suppress tumor growth via regulating the polarization of macrophages. We showed that E2 re-administration reduced tumor growth in orthotopic and ectopic mice HCC models. E2 functioned as a suppressor for macrophage alternative activation and tumor progression by keeping estrogen receptor β (ERβ) away from interacting with ATP5J (also known as ATPase-coupling factor 6), a part of ATPase, thus inhibiting the JAK1-STAT6 signaling pathway. These studies introduce a novel mechanism for suppressing male-predominant HCC.
肝癌（HCC）在男性中的发病率高于女性，但对其潜在的分子机制知之甚少。
我们发现 17β-雌二醇（E2）可以通过调节巨噬细胞的极化来抑制肿瘤生长。
雌激素作为巨噬细胞替代激活的抑制因子发挥作用。
这些研究为抑制男性高发 HCC 提供了一种新的机制。肝癌（HCC）是最恶性的癌症之一，在男性中的发病率明显高于女性；然而，其潜在的分子机制知之甚少。在这里，我们发现 17β-雌二醇（E2）可以通过调节巨噬细胞的极化来抑制肿瘤生长。我们表明，E2 的再给药减少了原位和异位小鼠 HCC 模型中的肿瘤生长。E2 通过使雌激素受体 β（ERβ）远离与 ATP 酶偶联因子 6（ATP5J，也称为 ATPase-coupling factor 6）相互作用，作为巨噬细胞替代激活和肿瘤进展的抑制剂，从而抑制 JAK1-STAT6 信号通路。这些研究为抑制男性高发 HCC 提供了一种新的机制。
