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* McGill Cancer Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6; and Carcinoembryonic antigen (CEA) is a tumor
marker that is overexpressed in many human cancers
and functions in vitro as a homotypic intercellular adhesion molecule. We have investigated the possibility of synergy between CEA, v-Myc, and Bcl-2 in the
transformation of cells with differentiation capacity.
We find that v-Myc increases the cell division rate and
maximum density of rat L6 myoblasts but also markedly stimulates both apoptosis and surprisingly, differentiation, thus preventing transformation. The superposition of Bcl-2 blocks the apoptotic stimulation of
v-Myc and independently promotes further cell division
at confluence, but still allows differentiation. The further expression of CEA has a dominant effect in blocking differentiation, regardless of the presence of the
other activated oncogenes, generating cells that enter a
reversible quiescent G0-like state in medium promoting
differentiation. Transfectants expressing CEA with or
without v-myc and bcl-2 allow the emergence of cells
with the property of heritable, efficient, anchorageindependent growth in soft agar and the ability to
markedly reduce the latency for tumor formation in
nude mice. We propose that by prolonging cell survival
in the presence of differentiation signals, CEA represents a novel class of dominant differentiation-blocking oncogene.
Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9
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