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Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation.

Screaton RA, Penn LZ, Stanners CP - J. Cell Biol. (1997)

Bottom Line: 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, anchorage-independent 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.

View Article: PubMed Central - PubMed

Affiliation: McGill Cancer Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.

ABSTRACT
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, anchorage-independent 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.

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Related in: MedlinePlus

Cell sizes of L6 transfectants corresponding to the  growth curve data of Fig. 2. Cell diameters, as determined by  pulse height analysis of particle count data, are shown.
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Figure 3: Cell sizes of L6 transfectants corresponding to the growth curve data of Fig. 2. Cell diameters, as determined by pulse height analysis of particle count data, are shown.

Mentions: To investigate the effects of v-Myc alone on the growth behavior of L6 myoblasts, M and P cells were seeded in replicate culture dishes in GM and their cell numbers determined daily without change of medium; the results for a single experiment typical of three separate experiments, which included transfectants expressing Bcl-2 and CEA (see below), are shown in Fig. 2. The population doubling times are revealed by the slopes of the curves and are reported along with initial (day 5) and final (day 15) saturation densities in the inset of Fig. 2. v-Myc expression increased both the proliferation rate and the maximum culture density (Fig. 2, inset, compare P and M). These relatively small differences were highly significant and reproducible in repeated experiments. Cells expressing v-Myc were reduced in size during the exponential growth phase (Fig. 3), which is consistent with the observed increase in proliferative rate (Murray and Hunt, 1993).


Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in cellular transformation.

Screaton RA, Penn LZ, Stanners CP - J. Cell Biol. (1997)

Cell sizes of L6 transfectants corresponding to the  growth curve data of Fig. 2. Cell diameters, as determined by  pulse height analysis of particle count data, are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139844&req=5

Figure 3: Cell sizes of L6 transfectants corresponding to the growth curve data of Fig. 2. Cell diameters, as determined by pulse height analysis of particle count data, are shown.
Mentions: To investigate the effects of v-Myc alone on the growth behavior of L6 myoblasts, M and P cells were seeded in replicate culture dishes in GM and their cell numbers determined daily without change of medium; the results for a single experiment typical of three separate experiments, which included transfectants expressing Bcl-2 and CEA (see below), are shown in Fig. 2. The population doubling times are revealed by the slopes of the curves and are reported along with initial (day 5) and final (day 15) saturation densities in the inset of Fig. 2. v-Myc expression increased both the proliferation rate and the maximum culture density (Fig. 2, inset, compare P and M). These relatively small differences were highly significant and reproducible in repeated experiments. Cells expressing v-Myc were reduced in size during the exponential growth phase (Fig. 3), which is consistent with the observed increase in proliferative rate (Murray and Hunt, 1993).

Bottom Line: 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, anchorage-independent 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.

View Article: PubMed Central - PubMed

Affiliation: McGill Cancer Centre and Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.

ABSTRACT
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, anchorage-independent 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.

Show MeSH
Related in: MedlinePlus