title: Oestrogen attenuates tumour progression in hepatocellular carcinoma.
abstract: The precise mechanisms underlying gender disparity in hepatocellular carcinoma (HCC) progression and prognosis are not understood. We demonstrate that oestrogen attenuates HCC progression in vitro and in vivo, and this may contribute to the gender differences in HCC behaviour. To investigate the role of oestrogen in HCC progression, we developed an orthotopic homograft tumour model by liver implantation of H22 cells. In combination with male castration, female ovariectomy, and oestrogen treatment, we tested the hypothesis that oestrogen contributes to gender disparity in this model. Pathological analyses were performed to examine the changes in biological behaviour of liver cancer cells, and two cell lines were used to investigate possible molecular mechanisms of the suppressive effect of oestrogen. Our data showed that oestrogen modulates HCC malignancy in vivo by reducing tumour cell invasion, arresting cell cycle progression, and promoting apoptosis, characterized by decreased expression of MMP-2, MMP-9, PCNA, cyclin A, cyclin D1, and Bcl-2, and increased expression in cleaved caspase 3. Through in vitro assays, we further confirmed the changes in expression levels of these related proteins, gained insights into the molecular cascades of oestrogen-induced HCC suppression, and indicated the oestrogen receptor α-mediated inhibition of NF-κB binding activity as a pivotal event in this process. This study represents a novel description of the mechanisms regarding the suppressive effects of oestrogen on HCC, adding a new understanding to the gender disparity in HCC progression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Model Animal Research Center, Nanjing University, Nanjing, China.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Xu
authors.forename: Yinna
authors.initials: Y
authors.lastname: Wei
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yichen
authors.initials: Y
authors.lastname: Xu
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
authors.forename: Renxiang
authors.initials: R
authors.lastname: Tan
authors.forename: Pingping
authors.initials: P
authors.lastname: Shen
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002369:Castration; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D004967:Estrogens / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008136:Longevity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D011485:Protein Binding / Q000187:drug effects; D012737:Sex Factors; D014184:Transplantation, Homologous
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004967:Estrogens; D016328:NF-kappa B