Growth inhibition and induction of apoptosis by HGF in transformed rat liver epithelial cells
Growth inhibition and induction of apoptosis by HGF in transformed rat liver epithelial cells
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DOI：
10.1006/bbrc.1997.6938
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发表时间：
1997-07-18
影响因子：
3.1
通讯作者：
Thorgeirsson, SS
中科院分区：
文献类型：
--
作者：
Conner, EA;Wirth, PJ;Thorgeirsson, SS
最近，我们在转基因小鼠模型中证明，肝细胞生长因子（HGF）可抑制 c-myc 依赖性肝癌发生。使用一系列大鼠肝上皮（RLE）细胞系进一步表征了 HGF 在致癌作用中的抑制作用，这些细胞系在体外用黄曲霉毒素或癌基因转化或自发转化。 HGF 在自发细胞和黄曲霉毒素转化细胞中产生细胞抑制作用并增强细胞运动性。在正常 RLE 细胞中，HGF 具有轻微刺激作用并且不会引起散射。所有细胞系中的 HGF 受体均被酪氨酸磷酸化，表明其具有功能活性并能够产生信号事件。在黄曲霉毒素转化的细胞中，HGF 还诱导细胞凋亡，与组成型 c-myc 表达和 1 Kb bax-alpha 转录物相关。这些发现表明，转化的 RLE 细胞系可能提供有用的模型来进一步研究 HGF 及其受体调节肿瘤发展的机制。 (C) 1997 年学术出版社。
Recently we demonstrated in a transgenic mouse model that hepatocyte growth factor (HGF) inhibits c-myc dependent hepatocarcinogenesis. The inhibitory effects of HGF in carcinogenesis were further characterized using a series of rat liver epithelial (RLE) cell lines which were transformed in vitro with either aflatoxin or oncogenes, or spontaneously. HGF caused a cytostatic effect and enhanced cell motility in spontaneously and aflatoxin-transformed cells. In normal RLE cells HGF was slightly stimulatory and did not induce scattering, The HGF receptor was tyrosine phosphorylated in all cell lines, indicating that it is functionally active and capable of signaling events. In the aflatoxin transformed cells HGF also induced apoptosis, associated with constitutive c-myc expression and 1 Kb bax-alpha transcripts. These findings indicate that transformed RLE cell lines may provide a useful model to further examine the mechanism(s) by which HGF and its receptor modulate neoplastic development. (C) 1997 Academic Press.