Ke Zunfu, Zhang Xiaowen, Ma Lanlan, Wang Liantang
Department of Pathology, Medical School of Sun Yat-sen University, Guangzhou 510080, Province Guangdong, PR China.
Hum Pathol. 2008 Oct;39(10):1438-45. doi: 10.1016/j.humpath.2008.03.006. Epub 2008 Jul 11.
Deleted in pancreatic carcinoma locus 4 influences tumorigenesis and tumor progression by various mechanisms, including apoptosis. The aim of this study is to determine whether deleted in pancreatic carcinoma locus 4 participates in apoptosis in lung cancer and clarify its relationship with clinical parameters of non-small cell lung cancer. Immunohistochemical results revealed that the positive rate of deleted in pancreatic carcinoma locus 4 in normal tracheal-bronchial epithelium (89.5%, 17/19) was much higher than that in tumor tissues (63.5%, 33/52) (P < .05) and closely correlated with lymph node metastasis (P < .001). These results were further confirmed by Western blot analysis. Furthermore, deleted in pancreatic carcinoma locus 4 overexpression was inversely associated with Bcl-2 immunostaining (P < .01), and the apoptosis index in deleted in pancreatic carcinoma locus 4-positive carcinomas (8.65 +/- 1.46) was much higher than that in deleted in pancreatic carcinoma locus 4-negative carcinomas (2.12 +/- 0.04) (P < .05). The results of deleted in pancreatic carcinoma locus 4 small interfering RNA in A549 cells also showed that deleted in pancreatic carcinoma locus 4 could inhibit cell proliferation, decrease Bcl-2 mRNA and protein expression, and increase Bax messenger RNA and protein expression. These findings indicated that Deleted in pancreatic carcinoma locus 4 might be an important biomarker for malignant transformation and be involved in inducing apoptosis by modulating Bcl-2/Bax balance.
胰腺癌缺失基因座4通过多种机制影响肿瘤发生和肿瘤进展，包括细胞凋亡。本研究旨在确定胰腺癌缺失基因座4是否参与肺癌细胞凋亡，并阐明其与非小细胞肺癌临床参数的关系。免疫组化结果显示，正常气管支气管上皮中胰腺癌缺失基因座4的阳性率（89.5%，17/19）远高于肿瘤组织（63.5%，33/52）（P<0.05），且与淋巴结转移密切相关（P<0.001）。蛋白质免疫印迹分析进一步证实了这些结果。此外，胰腺癌缺失基因座4的过表达与Bcl-2免疫染色呈负相关（P<0.01），胰腺癌缺失基因座4阳性癌的凋亡指数（8.65±1.46）远高于胰腺癌缺失基因座4阴性癌（2.12±0.04）（P<0.05）。A549细胞中胰腺癌缺失基因座4小干扰RNA的结果也表明，胰腺癌缺失基因座4可抑制细胞增殖，降低Bcl-2 mRNA和蛋白表达，并增加Bax信使核糖核酸和蛋白表达。这些发现表明，胰腺癌缺失基因座4可能是恶性转化的重要生物标志物，并通过调节Bcl-2/Bax平衡参与诱导细胞凋亡。
