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The embryonic environment strongly attenuates v-src oncogenesis in mesenchymal and epithelial tissues, but not in
A W Stoker1, C Hatier, M J Bissell
1Division of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Abstract:
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.
Insights
The oncogene v-src transforms cells in culture but not typically in embryos. Embryonic environments suppress v-src-induced neoplasia, highlighting the role of the in vivo environment in controlling cell growth.
Area of Science:
- Cell Biology
- Developmental Biology
- Oncology
Background:
- The oncogene v-src encodes a tyrosine kinase that can induce cell transformation.
- Cellular behavior is influenced by both genetic factors and the surrounding environment.
- Understanding how the in vivo environment affects oncogene activity is crucial for cancer research.
Purpose of the Study:
- To investigate the impact of the embryonic environment on v-src-induced cell transformation.
- To compare the effects of v-src expression in avian embryo cells in ovo versus in vitro.
- To identify environmental factors that may attenuate oncogene-driven neoplasia.
Main Methods:
- Replication-defective retroviral vectors expressing v-src and lacZ were used to infect avian embryo cells.
- Cells were analyzed both in culture (embryo fibroblasts) and within the developing embryo (stage-24 limbs).
- Cellular growth, morphology, differentiation, and tumor formation were assessed in both environments.
Main Results:
- In culture, v-src induced rapid morphological transformation, anchorage-independent growth, and tumorigenesis.
- In ovo, most v-src-expressing cell clones exhibited normal growth and differentiation, with attenuated neoplasia.
- Rare instances of hyperplasia, dysplasia, and rapid neoplasia (in primitive endothelium) were observed in ovo, indicating environmental modulation.
Conclusions:
- The embryonic environment plays a critical role in suppressing v-src-induced neoplastic transformation.
- Cells can maintain differentiation commitment despite oncogene expression within the developing embryo.
- Cultured cells may lose essential environmental cues present in vivo, leading to altered responses to oncogenes.