Liver hepatocyte growth factor does not always correlate with hepatocellular proliferation in human liver lesions: Its specific receptor c-met does

Liver hepatocyte growth factor does not always correlate with hepatocellular proliferation in human liver lesions: Its specific receptor c-met does
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DOI:
10.1053/jhep.1996.v24.pm0008707284
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发表时间:
1996-07-01
期刊:
影响因子:
13.5
通讯作者:
Grigioni, WF
Grigioni, WF
中科院分区:
医学1区
文献类型:
--
作者:
DErrico, A;Fiorentino, M;Grigioni, WF

文献摘要

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肝细胞生长因子(HGF)及其特异性受体c-met的表达水平增加已在几种良性和恶性病变的肝脏中显示,在实验模型和人类中均是如此。我们用免疫组化方法检测了20例肝细胞癌(HCC)、5例局灶性结节增生(FNH)、4例暴发性肝炎(FH)和1例再生肝中HGF和c-met原癌基因产物(c-met pp)的表达。c-met原癌基因产物在所有病例中表达,在HCC和导管化生中显著过表达。所有病例的Ito细胞和20例HCC中9例(45%)的肿瘤性肝细胞均检测到HGF。比较HGF和c-met原癌基因产物的表达水平与cyclin A阳性细胞核百分率的关系,c-met原癌基因产物与cyclin A阳性细胞核百分率的关系最密切。这似乎表明,独立于天然肝HGF的水平,c-met原癌基因产物是肝细胞增殖的最活跃的调节剂。
Increased levels of expression of hepatocyte growth factor (HGF) and its specific receptor c-met have been shown in the liver of several benign and malignant pathologies, both in experimental models and humans. We investigated by immunohistochemistry the presence of both HGF and c-met protooncogene product (c-met pp) in 20 hepatocellular carcinomas (HCCs), 5 focal nodular hyperplasias (FNHs), 4 cases of fulminant hepatitis (FH), and 1 case of regenerated liver. The c-met protooncogene product was expressed in all cases with marked overexpression in the HCCs and in ductular metaplasia. HGF was detected in the Ito cells of all cases and in neoplastic hepatocytes of 9 of 20 HCCs (45%), The proliferative index of each lesion was evaluated by means of the polyclonal antibody anti-cyclin A. When the level of expression of HGF and c-met protooncogene product with the percentage of cyclin A(+) nuclei were compared, the closest relationship was between c-met protooncogene product and cyclin A, In 11 of 20 HCCs (55%), there was no correlation between HGF positivity and cyclin A. This seems to suggest that, independently of the levels of native liver HGF, c-met protooncogene product is the most active modulator of liver cell proliferation.