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. 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.
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. 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.
Authors: M P Myers; J N Andersen; A Cheng; M L Tremblay; C M Horvath; J P Parisien; A Salmeen; D Barford; N K Tonks Journal: J Biol Chem Date: 2001-11-01 Impact factor: 5.157
Authors: M Barajas; G Mazzolini; G Genové; R Bilbao; I Narvaiza; V Schmitz; B Sangro; I Melero; C Qian; J Prieto Journal: Hepatology Date: 2001-01 Impact factor: 17.425
Authors: Shanshan Deng; Marco Ramos-Castaneda; Walter V Velasco; Michael J Clowers; Berenice A Gutierrez; Oscar Noble; Yiping Dong; Melody Zarghooni; Lucero Alvarado; Mauricio S Caetano; Shuanying Yang; Edwin J Ostrin; Carmen Behrens; Ignacio I Wistuba; Laura P Stabile; Humam Kadara; Stephanie S Watowich; Seyed Javad Moghaddam Journal: Carcinogenesis Date: 2020-11-13 Impact factor: 4.944
Authors: Laura Campbell; Elaine Emmerson; Helen Williams; Charis R Saville; Andrée Krust; Pierre Chambon; Kimberly A Mace; Matthew J Hardman Journal: J Invest Dermatol Date: 2014-04-09 Impact factor: 8.551