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J. Biol. Chem. 287 (48): 40140-40149

© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.


Background: Hepatocarcinoma cancer (HCC) occurs more often in men than in women, and little is known about its underlying molecular mechanisms.

Results: We identify that 17β-estradiol (E2) could suppress tumor growth via regulating the polarization of macrophages.

Conclusion: Estrogen functions as a suppressor for macrophage alternative activation.

Significance: These studies introduce a novel mechanism for suppressing male-predominant HCC.


Estrogen Represses Hepatocellular Carcinoma (HCC) Growth via Inhibiting Alternative Activation of Tumor-associated Macrophages (TAMs)*Formula

Weiwei Yang{ddagger}, Yan Lu{ddagger}, Yichen Xu{ddagger}, Lizhi Xu§, Wei Zheng{ddagger}, Yuanyuan Wu{ddagger}, Long Li{ddagger}, , and Pingping Shen{ddagger}1

From the {ddagger}State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center, Nanjing University, Nanjing 210093, China and
the §Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing 210093, China

ABSTRACT Back to Top

Abstract: 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.


Key Words: Estrogen • Estrogen Receptor • Macrophages • Tumor Immunology • Tumor Therapy • Alternatively Activated Macrophages • Hepatocellular Carcinoma • Tumor Progression • Tumor-associated Macrophages (TAMs) • Alternatively Activated Macrophage (M2)

Received for publication February 5, 2012. Revision received August 6, 2012.

1 To whom correspondence should be addressed. Tel.: 86-25-83686635; Fax: 86-25-83594060; E-mail: ppshen{at}nju.edu.cn.



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