EGF promotes in vivo tumorigenic growth of primary chicken embryo fibroblasts expressing v-myc and enhances in vitro transformation by the v-erbA oncogene.
We report that the activation of the endogenous chicken EGF receptor leads to the tumorigenic growth in vivo of early passage chicken embryo fibroblasts (CEFs) that express a nonsarcomagenic oncogene, v-myc. To provide a continuous paracrine source of this growth factor in vivo, we employed irradiated Rat-1 cells which had been stably transfected with a synthetic cDNA to human EGF. Expression of another non-sarcomagenic nuclear oncogene, v-erbA, prones the CEFs to in vitro transformation by EGF, but does not cause EGF dependent tumorigenicity in vivo. The short period of incubation in the in vivo assay employed by our study (10 days), together with the genetic stability of primary chicken embryo fibroblasts, make it very likely that the reported alterations in cellular behaviour are a direct and primary effect of the expression of the relevant oncogenes and their cooperation with the EGF induced response. Dose response and ligand binding assays suggest that the EGF response is transmitted via the chicken c-erbB molecule, which by virtue of its preference for TGF-alfa is distinct from the mammalian EGF receptors studied so far. The level of expression of the endogenous chicken EGF receptor is within the same range as that reported for primary human fibroblasts (5-7 x 10(3) per cell). The cooperative effect of v-myc with chicken c-erbB probably takes place at a post receptor level, as its expression did not affect the steady state level or affinity for ligand of the chicken EGF receptor.
Khazaie
K
K
Immuno-Virologie Moleculaire et Cellulaire, UMR 0005-CNRS-UCBL, Faculte de Medecine A. Carrel, Lyon, France.
Panayotou
G
G
Aguzzi
A
A
Samarut
J
J
Gazzolo
L
L
Jurdic
P
P
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002642:Chick Embryo; D003114:Colony-Forming Units Assay; D066246:ErbB Receptors / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000502:physiology*; D005822:Genetic Vectors; D066298:In Vitro Techniques; D018774:Oncogene Proteins v-erbA; D010957:Plasmids / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D014162:Transfection
D018774:Oncogene Proteins v-erbA; D015682:Retroviridae Proteins, Oncogenic; D066246:ErbB Receptors