RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line
RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line
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DOI：
10.1002/ijc.22328
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发表时间：
2007-02-01
影响因子：
6.4
通讯作者：
Sekido, Yoshitaka
中科院分区：
文献类型：
--
作者：
Sato, Naohito;Fukui, Takayuki;Sekido, Yoshitaka
癌细胞中纯合缺失的鉴定为肿瘤抑制基因（TSG）的定位提供了强有力的证据。我们分析了非小细胞肺癌（NSCLC）细胞系NCI-H2882的2p24纯合缺失，发现缺失大小为3.7 Mbp。由于RhoB被认为是候选TSG，位于该区域，我们分析了RhoB在NSCLC中的改变。虽然我们在48个细胞系中没有发现突变，包括20个NSCLC，但在128个原发性NSCLC中的杂合性丢失（洛）分析显示，62个信息样本中有25个在RhoB位点有洛。北方印迹分析28个细胞系（包括15个NSCLC）显示27个细胞系RhoB表达下调。我们分析了RhoB在112例原发性NSCLC中的表达，发现78例腺癌中有33例（42%）没有RhoB表达或RhoB表达较弱，而我们在31例鳞状细胞癌中发现了29例（94%）。RhoB无表达或弱表达在低分化或中分化腺癌中比在高分化腺癌中更常见（p = 0.0014）。此外，RhoB的无表达或弱表达表明患者预后不良的倾向。尽管在启动子区域没有发现高甲基化，但非小细胞肺癌细胞系中RhoB的表达是由组蛋白脱乙酰酶抑制诱导的，这表明RhoB下调可能是由于组蛋白修饰造成的。目前的研究表明，RhoB的表达经常下调NSCLC的多种机制，这表明RhoB是一个候选的TSG或NSCLC。(c)2006 Wiley-Liss，Inc.
Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCI-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed RhoB expression in 112 primary NSCLCs with immunohistochemistrv and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoB indicated a tendency to poor patient prognosis. Although hypermethylation was not to found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG or NSCLC. (c) 2006 Wiley-Liss, Inc.