Studies on the control of gene expression of the carcinoembryonic antigen family in human tissue.

The control of expression of genes of the carcinoembryonic antigen family was investigated in 22 specimens of malignant and nonmalignant human colonic tissues. These surgical specimens included seven colonic adenocarcinomas that were compared with normal adjacent colonic mucosal tissues from the same individual. mRNA preparations from all colonic tissues expressed three bands of 3.5, 3.0, and 2.6 kilobases on Northern blots probed with carcinoembryonic antigen (CEA) complementary 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 2- to greater than 100-fold. Furthermore, there was no direct proportionality between mRNA levels and gene product expression, suggesting that the known variations in CEA expression in human colonic 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.