Carcinoembryonic antigen regulation in human colorectal tumor cells by a site‐selective cyclic amp analogue: A comparison with interferon‐gamma

Treatment of human colorectal tumor cells (LS174T, HT29, and WIDr) with analogues of cyclic AMP (cAMP) (dibutyryl‐cAMP and 8‐Cl‐cAMP) selectively enhances the expression of carcinoembryonic antigen (CEA). Dose and temporal kinetics results revealed that 8‐Cl‐cAMP was approximately 100‐fold more potent than dibutyryl‐cAMP for increasing CEA expression. Results demonstrated that 8‐Cl‐cAMP treatment of LS174T quantitatively increased CEA levels in cell extracts 2‐fold, increased anti‐CEA monoclonal antibody (MAb) binding to the tumor cell surface, and induced the appearance of CEA‐related mRNA transcripts. The findings suggest that 8‐Cl‐cAMP is capable of regulating CEA expression at transcriptional and/or post‐transcriptlonal levels. Other human tumor cells, as well as normal cell types which do not constitutively express CEA, remained CEA‐negative following 8‐Cl‐cAMP treatment. Moreover, the level of expression of other human tumor antigens as well as antigens of the major histocompatibility complex were not changed by 8‐Cl‐cAMP treatment, suggesting some selectivity for CEA regulation by this cAMP analogue. In vivo administration of 8‐Cl‐cAMP to athymic mice bearing LS174T tumor xenografts increased the amount of anti‐CEA MAb bound to tumor extracts as well as the tumor localization of a radlonuclideconjugated anti‐CEA MAb. The results indicate that 8‐Cl‐cAMP can selectively upregulate CEA expression on human colorectal tumor cells in vitro and in vivo. Interestingly, IFN‐γ treatment of the LS174T cells falls to enhance or induce expression of CEA or any of the histocompatibility leukocyte antigens. Thus, 8‐Cl‐cAMP treatment regulates CEA expression through another cellular pathway which may involve cAMP‐dependent protein kinase.