Overexpression of the RON gene in human breast carcinoma
Overexpression of the RON gene in human breast carcinoma
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DOI：
10.1038/sj.onc.1201812
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发表时间：
1998-06-04
期刊：
影响因子：
8
通讯作者：
Comoglio, PM
中科院分区：
文献类型：
--
作者：
Maggiora, P;Marchio, S;Comoglio, PM
RON基因是巨噬细胞刺激蛋白酪氨酸激酶受体(也称为散射因子2)的编码基因，其结构性激活在体外可诱导侵袭-转移表型。到目前为止，关于这个新的Met癌基因家族成员在自发发生的人类癌症中的表达尚不清楚。在此，我们报告了RON在约50%的原发乳腺癌(35/74例)中的异常高表达。其中，12例的表达增加了20倍以上，过度表达的蛋白在酪氨酸残基上发生了结构性的磷酸化。值得注意的是，RON仅在乳腺上皮细胞中几乎检测到，其在良性乳腺病变(包括腺瘤和乳头状瘤)中的表达保持不变。在不同组织类型的癌中观察到过表达；它与疾病的任何阶段相关，并与绝经后状态相关。在体外培养的乳腺癌细胞中，RON受体的激活导致了重组基底膜的增殖、迁移和侵袭。总之，这些数据表明RON基因在人类乳腺癌向侵袭-转移表型发展过程中起作用。
Constitutive activation of the RON gene, known to code for the tyrosine-kinase receptor for Macrophage Stimulating Protein (also known as Scatter Factor 2), has been shown to induce invasive-metastatic phenotype in vitro. As yet, nothing is known about the expression of this novel member of the MET-oncogene family in spontaneously occurring human cancers. Here we report that Ron is expressed at abnormally high levels in about 50% primary breast carcinomas (35/74 patients). Among these, the expression is increased more than 20-fold in 12 cases and the overexpressed protein is constitutively phosphorylated on tyrosine residues. Notably, Ron is only barely detectable in epithelial cells of the mammary gland, and its expression remains unchanged in benign breast lesions (including adenomas and papillomas). Overexpression was observed in different histotypic variants of carcinomas; it is associated with the disease at any stage and correlates with the post-menopausal status. In breast carcinoma cells grown im vitro, activation of the Ron receptor resulted in proliferation, migration and invasion through reconstituted basement membranes. Altogether, these data suggest a role for the RON gene in progression of human breast carcinomas to the invasive-metastatic phenotype.