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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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Tumorigenicity of L6 transfectants. The average latent  period in weeks of the different transfectant cell lines for tumor  formation is displayed as solid bars. Results represent the average of two separate experiments. MBC-m is a cell population  generated by pooling four different MBC macrocolonies isolated  from soft agar and is termed MBC-mpool#1 in Table I.
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Figure 9: Tumorigenicity of L6 transfectants. The average latent period in weeks of the different transfectant cell lines for tumor formation is displayed as solid bars. Results represent the average of two separate experiments. MBC-m is a cell population generated by pooling four different MBC macrocolonies isolated from soft agar and is termed MBC-mpool#1 in Table I.

Mentions: The transformation potential of M cells was determined in vitro using a soft agar assay to assess the loss of anchorage dependence of growth. M cells formed colonies in soft agar with an efficiency of 1%, whereas P cells were incapable of anchorage-independent growth (Table I). No macrocolonies of >500 cells were formed by either P or M cells. Thus, v-Myc alone does not induce a highly transformed phenotype, consistent with previous results of Falcone et al. (1985) with v-Myc transformed quail myoblasts. Moreover, v-myc expression had no effect on the latency of tumor formation in nude mice (see Fig. 9). We hypothesized that the failure of v-Myc to enhance transformation and tumorigenicity was due to the differentiation and death responses observed in v-myc–expressing myoblast monolayer cultures in depleted GM or in DM, which would compound the effect of decreasing local growth factor concentrations during colony growth. From these data we conclude that v-Myc stimulates the cell cycle “engine” of L6 cells, yet the concomitant increase in the potential to differentiate or die aborts full transformation.


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)

Tumorigenicity of L6 transfectants. The average latent  period in weeks of the different transfectant cell lines for tumor  formation is displayed as solid bars. Results represent the average of two separate experiments. MBC-m is a cell population  generated by pooling four different MBC macrocolonies isolated  from soft agar and is termed MBC-mpool#1 in Table I.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 9: Tumorigenicity of L6 transfectants. The average latent period in weeks of the different transfectant cell lines for tumor formation is displayed as solid bars. Results represent the average of two separate experiments. MBC-m is a cell population generated by pooling four different MBC macrocolonies isolated from soft agar and is termed MBC-mpool#1 in Table I.
Mentions: The transformation potential of M cells was determined in vitro using a soft agar assay to assess the loss of anchorage dependence of growth. M cells formed colonies in soft agar with an efficiency of 1%, whereas P cells were incapable of anchorage-independent growth (Table I). No macrocolonies of >500 cells were formed by either P or M cells. Thus, v-Myc alone does not induce a highly transformed phenotype, consistent with previous results of Falcone et al. (1985) with v-Myc transformed quail myoblasts. Moreover, v-myc expression had no effect on the latency of tumor formation in nude mice (see Fig. 9). We hypothesized that the failure of v-Myc to enhance transformation and tumorigenicity was due to the differentiation and death responses observed in v-myc–expressing myoblast monolayer cultures in depleted GM or in DM, which would compound the effect of decreasing local growth factor concentrations during colony growth. From these data we conclude that v-Myc stimulates the cell cycle “engine” of L6 cells, yet the concomitant increase in the potential to differentiate or die aborts full transformation.

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