Levin W J, Press M F, Gaynor R B, Sukhatme V P, Boone T C, Reissmann P T, Figlin R A, Holmes E C, Souza L M, Slamon D J
Department of Medicine, UCLA School of Medicine 90024, USA.
Oncogene. 1995 Oct 5;11(7):1261-9.
In 1995, there will be 172,000 new cases of lung cancer diagnosed and 153,000 deaths from this disease in the United States. While the pathogenesis of the disease process is poorly understood, a growing body of evidence suggests that abnormalities in cellular regulatory genes may play an important role in the induction, maintenance and/or progression of some tumor types. These genes include both growth promoting oncogenes as well as growth inhibitory or suppressor genes. Included among these genetic sequences are several cellular transcription factors. A group of these factors including c-jun, c-fos and EGR1 are members of a class of genes known as immediate early genes whose expression are inducible by a variety of stimuli including mitogenic and differentiation inducing growth factors, indicating a potential important role for these genes in normal growth processes. Since these genes are involved in early regulation of cellular growth properties and at least two (c-jun and c-fos) can act as oncogenes, we wished to determine whether their expression levels were altered in human non-small cell lung cancers (NSCLC) compared to normal lung tissue. To address this, Northern blot analyses were performed using c-fos, c-jun and EGR1 probes on RNA extracted from 101 NSCLC tumor specimens and adjacent uninvolved lung tissue. Analysis of this cohort revealed that 72% of the normal tissues demonstrate significantly greater expression of these transcription factors as compared to adjacent malignant tissue. Moreover, this expression pattern appeared to be coordinate for all three genes in the majority of cases. This differential expression pattern was confirmed at the protein level using an immunohistochemical approach with antibodies directed against the c-jun, c-fos and EGR1 gene products. Southern blot analyses demonstrated no gross alterations of these sequences at the DNA level, indicating that the observed differential expression pattern was not due to gross structural changes in the genes. These data suggest that down-regulation of these genes may be involved in the pathogenesis of lung cancer.
1995年，美国将有17.2万例新确诊的肺癌病例，15.3万人死于该疾病。虽然对该疾病进程的发病机制了解甚少，但越来越多的证据表明，细胞调节基因的异常可能在某些肿瘤类型的诱导、维持和/或进展中起重要作用。这些基因包括促进生长的癌基因以及生长抑制基因或抑癌基因。这些基因序列中包括几种细胞转录因子。其中一组因子包括c-jun、c-fos和EGR1，它们是一类被称为即刻早期基因的成员，其表达可被多种刺激诱导，包括有丝分裂原和诱导分化的生长因子，这表明这些基因在正常生长过程中可能具有重要作用。由于这些基因参与细胞生长特性的早期调节，并且至少有两个（c-jun和c-fos）可以作为癌基因，我们希望确定与正常肺组织相比，它们在人类非小细胞肺癌（NSCLC）中的表达水平是否发生改变。为了解决这个问题，我们使用c-fos、c-jun和EGR1探针，对从101例NSCLC肿瘤标本和相邻未受累肺组织中提取的RNA进行了Northern印迹分析。对该队列的分析显示，与相邻的恶性组织相比，72%的正常组织中这些转录因子的表达明显更高。此外，在大多数情况下，这三种基因的表达模式似乎是协同的。使用针对c-jun、c-fos和EGR1基因产物的抗体，通过免疫组织化学方法在蛋白质水平上证实了这种差异表达模式。Southern印迹分析表明，这些序列在DNA水平上没有明显改变，这表明观察到的差异表达模式不是由于基因的总体结构变化所致。这些数据表明，这些基因的下调可能与肺癌的发病机制有关。
