Zhou J, Nong L, Wloch M, Cantor A, Mulshine J L, Tockman M S
Molecular Screening Laboratory, H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33613, USA.
Lung Cancer. 2001 Dec;34(3):341-50. doi: 10.1016/s0169-5002(01)00254-9.
We have reported that a mouse monoclonal antibody, 703D4, which recognizes heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) can frequently detect lung cancer in exfoliated sputum epithelial cells 1-2 years earlier than routine chest X-ray or sputum cytomorphology. We along with others have shown that microsatellite alteration (MA) at selected loci can be recognized in sputum cells prior to clinical lung cancer. The present study was undertaken to determine how frequently the expression of hnRNP-A2/B1 message is associated with neoplastic clonal expansion as shown by MA in 41 cases of non-small cell lung cancer (NSCLC). We used Northern blotting to evaluate hnRNP-A2/B1 mRNA expression in lung tumor and remote noninvolved lung. We evaluated microsatellite instability (i.e. shifts; MI) or loss of heterozygosity (LOH) with a panel of 13 microsatellite markers at loci identified previously as susceptible in NSCLC. Of the 41 tumors, 25 (61%) over-expressed hnRNP-A2/B1 and 33 (80%) demonstrated MA in at least one of 13 loci (58% in at least two loci). The association between MA (one locus) and the overexpression of hnRNP-A2/B1 is statistically significant (P=0.0082), and those lung tumors with MA at two or more loci were significantly more likely to over-express hnRNP-A2/B1 mRNA (P=0.004). MA of loci on 3p were the only MA statistically associated with hnRNP-A2/B1 message overexpression (P=0.001). We conclude that lung tumor cells undergoing clonal expansion frequently upregulate hnRNP-A2/B1.
我们曾报道，一种识别不均一核核糖核蛋白A2/B1（hnRNP - A2/B1）的小鼠单克隆抗体703D4，能够比常规胸部X线检查或痰液细胞形态学检查提前1 - 2年在脱落的痰液上皮细胞中频繁检测到肺癌。我们和其他研究人员已经表明，在临床肺癌出现之前，痰液细胞中可识别出特定位点的微卫星改变（MA）。本研究旨在确定在41例非小细胞肺癌（NSCLC）中，hnRNP - A2/B1信息的表达与如MA所示的肿瘤性克隆扩增相关的频率。我们使用Northern印迹法评估肺肿瘤和远处未受累肺组织中hnRNP - A2/B1 mRNA的表达。我们用一组13个微卫星标记评估微卫星不稳定性（即移位；MI）或杂合性缺失（LOH），这些标记位于先前确定在NSCLC中易发生改变的位点。在41个肿瘤中，25个（61%）过度表达hnRNP - A2/B1，33个（80%）在13个位点中的至少一个位点显示MA（58%在至少两个位点）。MA（一个位点）与hnRNP - A2/B1的过度表达之间的关联具有统计学意义（P = 0.0082），并且在两个或更多位点有MA的肺肿瘤更有可能过度表达hnRNP - A2/B1 mRNA（P = 0.004）。3p位点的MA是唯一与hnRNP - A2/B1信息过度表达有统计学关联的MA（P = 0.001）。我们得出结论，经历克隆扩增的肺肿瘤细胞经常上调hnRNP - A2/B1。
