The embryonic environment strongly attenuates v-src oncogenesis in mesenchymal and epithelial tissues, but not in endothelia.
We demonstrate that the behavior of cells expressing v-src, a tyrosine kinase oncogene, differs profoundly between the embryonic and culture environments. V-src was introduced into avian embryo cells both in culture and in stage-24 embryo limbs, using replication-defective retroviral vectors. These vectors were used as single-hit, cellular markers to determine the environmental influences imposed by normal cells and tissues on clonal cell growth. The marker gene lacZ was coexpressed with v-src in order to locate the descendent cells. In culture, v-src induced rapid morphological transformation and anchorage-independent growth of embryo fibroblasts; the vectors were also tumorigenic in hatchling chickens. In contrast, most of the cell clones expressing v-src in the embryo grew normally without neoplasia. Expression of v-src vectors could be found in a wide range of cell types, demonstrating not only that neoplastic transformation is attenuated in ovo, but also that differentiation commitment in many lineages can be maintained concurrently with oncogene expression. Significantly, the embryonic control of cell growth could be perturbed by v-src under certain conditions. Rare, marked clones showed hyperplasia or dysplasia, and the primitive endothelium could succumb to rapid neoplasia; thus, these embryonic tissues are not inherently deficient in transformation factors. We propose that the environmental conditions imposed on cells in ovo are critical for the attenuation of neoplasia, while cultured cells lose this requisite environment.
Stoker
A W
AW
Division of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Hatier
C
C
Bissell
M J
MJ
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D002999:Clone Cells; D005314:Embryonic and Fetal Development; D004727:Endothelium / Q000166:cytology / Q000201:enzymology; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D015870:Gene Expression; D005822:Genetic Vectors; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)