EXPRESSION PATTERNS OF IMMEDIATE-EARLY TRANSCRIPTION FACTORS IN HUMANNONSMALL CELL LUNG-CANCER

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 patho genesis of the disease profess 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 progressi on of some tumor types. These genes include both growth promoting onco genes as well as growth inhibitory or suppressor genes. Included among these genetic sequences are several cellular transcription factor. 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 i nducible by a variety of stimuli including mitogenic and differentiati on 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 t heir expression levels were altered in human non-small cell lung cance rs (NSCLC) compared to normal lung tissue. To address this, Northern b lot 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 tissue s demonstrate significantly greater expression of these transcription factors as compared to adjacent malignant tissue. Moreover, this expre ssion pattern appeared to be coordinate for all three genes in the maj ority of cases. This differential expression pattern was confirmed at the protein level using an immunohistochemical approach with antibodie s directed against the c-jun, c-fos and EGR1 gene products. Southern b lot analyses demonstrated no gross alterations of these sequences at t he DNA level, indicating that the observed differential expression pat tern was not due to gross structural changes in the genes. These data suggest that downregulation of these genes may be involved in the path ogenesis of lung cancer.