Aberrant Estrogen Receptor alpha Expression Correlates with Hepatocellular Carcinoma Metastasis and its Mechanisms

作者:Sheng, Mao-Lin; Xu, Ge-Liang*; Zhang, Chuan-Hai; Jia, Wei-Dong; Ren, Wei-Hua; Liu, Wen-Bin; Zhou, Teng; Wang, Yong-Cang; Lu, Zheng-Lei; Liu, Wei-Feng; Dong, Xun-Zhong; Wang, Xiu-Jun; Lv, Yang
来源:Hepato-Gastroenterology, 2014, 61(129): 146-150.
DOI:10.5754/hge11859

摘要

Background/Aims: Metastasis remains one of the obstacles before poor prognosis of hepatocellular carcinoma (HCC) is improved. Estrogen receptor alpha (ER alpha) plays an important role in the development and progression of HCC. However, the molecular mechanism of ERa in mediating HCC metastasis is still unclear. The aim of the present study was to detect aberrant ER alpha expression in HCC and elucidate its possible mechanisms in HCC metastasis. Methodology: We detected expression of ER alpha, phospho-estrogen receptor alpha (p-ER alpha), nuclear factor kappa B (NF-kappa B) p65 and IVIatrix 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 ER alpha and p-ER alpha 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-kappa B p65 and MMP-9 was higher in HCC with PVTT than those without PVTT. The expression of NF-kappa B p65 and MMP-9 in HCC cells was also analogous to the tissues. Conclusions: These results demonstrated that expression of ER alpha, p-ER alpha, NF-kappa B p65 and MMP-9 correlated with invasion and metastasis in HCC. The mechanism of HCC metastasis may mediate through cross-talk between the NF-kappa B and ER signaling pathways. Meanwhile, ER alpha regulated MMP-9 through NF-kappa B indirectly.