Loss of RhoB expression in human lung cancer progression
Loss of RhoB expression in human lung cancer progression
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DOI：
10.1158/1078-0432.ccr-03-0149
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发表时间：
2004-04-15
影响因子：
11.5
通讯作者：
Favre, G
中科院分区：
文献类型：
--
作者：
Mazieres, J;Antonia, T;Favre, G
目的：RhoB是一种属于RAS蛋白超家族的低分子量GTP酶。虽然大多数Rho蛋白已被证明在增殖和恶性转化中起积极作用，但RhoB的具体作用似乎有更大的分歧。我们以前曾报道过RhoB抑制多种人类癌细胞的增殖。在这里，我们研究了RhoB在人类肺癌中所起的特定作用。实验设计：我们通过两个大型的独立研究，分别对94个和45个样本进行免疫染色，分析了从正常到浸润性肺癌不同组织类型的人肺组织中RhoB蛋白的表达。然后，我们研究了RhoB过表达在肺癌(A549，腺癌)模型中的细胞效应和在裸鼠体内的致瘤性。结果：在两项研究中，RhoB蛋白在正常肺组织中都有表达，随着肺癌的进展，RhoB蛋白的表达显著降低(P<；0.01)。有趣的是，与非肿瘤上皮相比，96%的浸润性肿瘤中RhoB的表达缺失，而在低分化肿瘤中RhoB的表达减少86%。此外，RhoB的表达缺失与肿瘤分期和增殖指数显著相关，而与P53和Bcl2的表达无相关性。结论：肺癌细胞系A549中RhoB基因的异位表达可抑制细胞增殖、非贴壁生长和裸鼠移植瘤生长。结论：RhoB基因的表达缺失在肺癌发生过程中非常常见，增强了其潜在的抑瘤活性，提高了其在肿瘤治疗中的潜在应用价值。
Purpose: RhoB is a low molecular weight GTPase belonging to the Ras protein superfamily. Whereas most Rho proteins have been shown to have a positive role in proliferation and malignant transformation, the specific role of RhoB appears more divergent. We reported previously that RhoB inhibits cell proliferation in various human cancer cells. Here, we studied the specific role played by RhoB in human lung cancer.Experimental Design: We analyzed the expression of RhoB protein by immunostaining in human lung tissues ranging from normal to invasive carcinoma from different histological types in two large independent studies of, respectively, 94 and 45 samples. We then studied the cellular effect of RhoB overexpression in a model of lung cancer (A549, adenocarcinoma) and tumorigenicity in nude mice.Results: We showed in both studies that RhoB protein was expressed in normal lung and decreased dramatically through lung cancer progression (P < 0.01). Interestingly, RhoB expression was lost in 96% of invasive tumors and reduced by 86% in poorly differentiated tumors compared with the nonneoplastic epithelium. Moreover, the loss of expression of RhoB correlated significantly with tumor stage and proliferative index, whereas no correlation was found between RhoB and p53 or Bcl-2 expression. We then showed that ectopic expression of RhoB in lung cancer cell line A549 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth in nude mice.Conclusions: RhoB loss of expression occurs very frequently in lung carcinogenesis, reinforcing its putative tumor suppressive activity, and raising the value of its potential use in cancer therapy.