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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

Immunoblot analysis of parental and total transfectant  cell populations. Total protein lysates were separated by SDSPAGE and transferred to a membrane for immunodetection using (A) pan-myc and (B) Bcl-2 polyclonal antisera. Lane assignments are as follows: P, parental L6, M, v-Myc+ cells, B, Bcl-2+  cells. Migration of molecular weight (kD) markers is shown.
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Figure 1: Immunoblot analysis of parental and total transfectant cell populations. Total protein lysates were separated by SDSPAGE and transferred to a membrane for immunodetection using (A) pan-myc and (B) Bcl-2 polyclonal antisera. Lane assignments are as follows: P, parental L6, M, v-Myc+ cells, B, Bcl-2+ cells. Migration of molecular weight (kD) markers is shown.

Mentions: The block in myogenic differentiation of L6 cells stably expressing CEA in DM (Eidelman et al., 1993) led to the hypothesis that ectopic CEA expression could contribute to transformation of myoblasts in conjunction with a proliferative stimulus provided by an activated oncogene. Avian v-Myc and its cellular homolog, c-Myc, are cell cycle activators that promote G0–G1 and G1–S transitions (Evan and Littlewood, 1993, and references therein). Pooled populations of L6 cells stably expressing v-Myc in a retroviral vector conferring hygromycin B resistance (M) or of L6 cells expressing the drug resistance gene of the vector alone (P, parental) were therefore generated; expression of the p110 gag–v-Myc viral protein was verified by immunoblot (Fig. 1 A).


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)

Immunoblot analysis of parental and total transfectant  cell populations. Total protein lysates were separated by SDSPAGE and transferred to a membrane for immunodetection using (A) pan-myc and (B) Bcl-2 polyclonal antisera. Lane assignments are as follows: P, parental L6, M, v-Myc+ cells, B, Bcl-2+  cells. Migration of molecular weight (kD) markers is shown.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Immunoblot analysis of parental and total transfectant cell populations. Total protein lysates were separated by SDSPAGE and transferred to a membrane for immunodetection using (A) pan-myc and (B) Bcl-2 polyclonal antisera. Lane assignments are as follows: P, parental L6, M, v-Myc+ cells, B, Bcl-2+ cells. Migration of molecular weight (kD) markers is shown.
Mentions: The block in myogenic differentiation of L6 cells stably expressing CEA in DM (Eidelman et al., 1993) led to the hypothesis that ectopic CEA expression could contribute to transformation of myoblasts in conjunction with a proliferative stimulus provided by an activated oncogene. Avian v-Myc and its cellular homolog, c-Myc, are cell cycle activators that promote G0–G1 and G1–S transitions (Evan and Littlewood, 1993, and references therein). Pooled populations of L6 cells stably expressing v-Myc in a retroviral vector conferring hygromycin B resistance (M) or of L6 cells expressing the drug resistance gene of the vector alone (P, parental) were therefore generated; expression of the p110 gag–v-Myc viral protein was verified by immunoblot (Fig. 1 A).

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