CARCINOEMBRYONIC ANTIGEN, A HUMAN TUMOR-MARKER, COOPERATES WITH MYC AND BCL-2 IN CELLULAR-TRANSFORMATION

Carcinoembryonic antigen (CEA) is a tumor marker that is overexpressed in many human cancers and functions in vitro as a homotypic intercell ular adhesion molecule. We have investigated the possibility of synerg y between CEA, v-Myc, and Bcl-2 in the transformation of cells with di fferentiation capacity. We find that v-Myc increases the cell division rate and maximum density of rat L6 myoblasts but also markedly stimul ates both apoptosis and surprisingly, differentiation, thus preventing transformation. The superposition of Bcl-2 blocks the apoptotic stimu lation of v-Myc and independently promotes further cell division at co nfluence, but still allows differentiation. The further expression of CEA has a dominant effect in blocking differentiation, regardless of t he presence of the other activated oncogenes, generating cells that en ter a ing reversible quiescent G(0)-like state in medium promoting dif ferentiation. Transfectants expressing CEA with or without v-myc and b cl-2 allow the emergence of cells with the property of heritable, effi cient, anchorage-independent growth in soft agar and the ability to ma rkedly reduce the latency for tumor formation in nude mice. We propose that by prolonging cell survival in the presence of differentiation s ignals, CEA represents a novel class of dominant differentiation-block ing oncogene.