title: Aberrant estrogen receptor alpha expression correlates with hepatocellular carcinoma metastasis and its mechanisms.
abstract: OBJECTIVE
  Metastasis one of the obstacles before poor prognosis of hepatocellular carcinoma (HCC) is improved. Estrogen receptor alpha (ERalpha) plays an important role in the development and progression of HCC. However, the molecular mechanism of ERalpha in mediating HCC metastasis is still unclear. The aim of the present study was to detect aberrant ERalpha expression in HCC and elucidate its possible mechanisms in HCC metastasis.
  
  
  METHODS
  We detected expression of ERalpha, phospho-estrogen receptor alpha (p-ERalpha), nuclear factor kappa B (NF-kappaB) p65 and Matrix metalloproteinase-9 (MMP-9) between HCC tissues with portal vein tumor thrombus (PVTT) and those without PVTT by immunohistochemical method. Moreover, the expression of above parameters was also determined in HCC cells of different metastatic potential by using immunocytochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) methods.
  
  
  RESULTS
  The expression of ERalpha and p-ERalpha was lower in HCC with PVTT than those without PVTT. Meanwhile, the expression pattern of above parameters was also similar in HCC cells of different metastatic potential, whereas, the expression of NF-kappaB p65 and MMP-9 was higher in HCC with PVTT than those without PVTT. The expression of NF-kappaB p65 and MMP-9 in HCC cells was also analogous to the tissues.
  
  
  CONCLUSIONS
  These results demonstrated that expression of ERalpha, p-ERalpha, NF-kappaB p65 and MMP-9 correlated with invasion and metastasis in HCC. The mechanism of HCC metastasis may mediate through cross-talk between the NF-KB and ER signaling pathways. Meanwhile, ERa regulated MMP-9 through NF-kappaB indirectly.
authors.forename: Mao-Lin
authors.initials: ML
authors.lastname: Sheng
authors.forename: Ge-Liang
authors.initials: GL
authors.lastname: Xu
authors.forename: Chuan-Hai
authors.initials: CH
authors.lastname: Zhang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Jia
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Ren
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Liu
authors.forename: Teng
authors.initials: T
authors.lastname: Zhou
authors.forename: Yong-Cang
authors.initials: YC
authors.lastname: Wang
authors.forename: Zheng-Lei
authors.initials: ZL
authors.lastname: Lu
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Liu
authors.forename: Xun-Zhong
authors.initials: XZ
authors.lastname: Dong
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059016:Tumor Microenvironment
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D016328:NF-kappa B; D020780:Matrix Metalloproteinase 9