Membrane localization of v-ErbB is required but not sufficient for ligand-independent transformation
| Autor: | Nita J. Maihle, Margaret A. Adelsman, Trace A. Christensen, Denise C. Connolly, Courtney A. Lovejoy, Andrew J. Danielsen |
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| Rok vydání: | 2004 |
| Předmět: |
animal structures
Mutant Chick Embryo Gene mutation Ligands Cell Line Viral vector Transformation Genetic Retrovirus ErbB Neoplasms Animals Oncogene biology Cell Membrane Oncogene Proteins v-erbB Cell Biology Fibroblasts biology.organism_classification Protein Transport Transmembrane domain Cell Transformation Neoplastic Animals Newborn Phosphoprotein Mutation Mutagenesis Site-Directed Cancer research Chickens |
| Zdroj: | Experimental Cell Research. 296:285-293 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2004.01.023 |
| Popis: | The v-ErbB retroviral oncogene is a transduced, mutated copy of the avian EGF receptor gene, and its expression is sufficient to induce tumor formation in vivo. The structural alterations that release the oncogenic potential of the v-ErbB oncogene are similar to EGFR gene mutations described in human tumors. Thus, the study of v-ErbB tumor biology offers a useful model through which we can gain insight into the mechanism of EGFR-induced malignancies. Despite years of study, however, questions remain regarding the domains of v-ErbB required for oncogenicity. We sought to clarify the role of the transmembrane domain of v-ErbB during transformation using S3-v-ErbB, an acutely transforming retroviral oncogene isolated from avian sarcomas. Infection of primary fibroblasts with a retroviral vector containing S3-v-ErbB results in the formation of a transformation-associated phosphoprotein signaling complex, soft agar colony formation, and the rapid induction of highly vascularized sarcomas in vivo. To address contribution of the transmembrane domain of S3-v-ErbB during these processes, we constructed a mutant version of this oncogene with a precise deletion in this domain. Specifically, the S3-v-ErbB-TM− mutant was created through an in-frame deletion of the entire transmembrane domain. Primary fibroblasts expressing this S3-v-ErbB-TM− mutant fail to form a characteristic transformation-associated phosphoprotein complex and do not grow in an anchorage-independent manner. In addition, day-old chicks injected with a helper-independent retrovirus expressing the S3-v-ErbB-TM− mutant exhibit only limited tumor formation in vivo. These results demonstrate that the transmembrane domain and, consequently membrane localization, are essential for S3-v-ErbB-mediated transformation. |
| Databáze: | OpenAIRE |
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