Studies on the Control of Gene Expression of the Carcinoembryonic Antigen Family in Human Tissue1

The control of expression of genes of the Carcinoembryonic antigen family was investigated in 22 specimens of malignant and nonmalignant human colonie tissues. These surgical specimens included seven colonie adenocarcinomas that were compared with normal adjacent colonie mu cosa! tissues from the same individual. mRNA preparations from all colonie tissues expressed three bands of 3.5, 3.0, and 2.6 kilobases on Northern blots probed with Carcinoembryonic antigen (CEA) comple mentary DNA probe while normal liver and spleen were negative. The major band of 3.0 kilobases was 6 to 10 times more intense in the colon tumor specimens than in the matched normal mucosa. However, the tumor/normal ratios of immunoreactive CEA in these pairs varied from 2to greater than 100-fold. Furthermore, there was no direct proportion ality between mRNA levels and gene product expression, suggesting that the known variations in CEA expression in human colonie tissues result from both transcriptional and posttranscriptional control mechanisms. Southern blots of DNA from these specimens did not reveal any gene rearrangements or amplifications accompanying expression. Finally, Southern blots of DNA digested with methylation-sensitive endonucleases and probed with a genomic DNA fragment upstream of CEA gene coding regions demonstrated that CEA expression is correlated with a decreased level of methylation in the 5' region of the CEA gene.