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[V-erbA oncogene, model of oncogenic activation of hormone receptor]
1Laboratoire de Biologie Moléculaire et Cellulaire, CNRS UMR49, INRA, Ecole Normale Supérieure de Lyon.
Abstract:
The identification of the viral oncogene v-erbA carried by an avian leukemia retrovirus has directly demonstrated the involvement of hormone receptors in neoplastic transformation. v-erbA represents an altered form of a nuclear receptor of the thyroid hormone T3. It blocks the differentiation of chicken erythrocyte progenitor cells and contributes to sarcoma transformation in association with other oncogenes. The protein encoded by v-erbA behaves as an antagonist against the normal T3 receptors and retinoic acid receptors. The primary effects of the protein result in altering the transcription of genes normally under control of the intact receptors. Presumably among these target genes are to be found genes which control cell differentiation and proliferation.
Insights
The viral oncogene v-erbA, an altered thyroid hormone receptor, drives cancer by blocking cell differentiation and altering gene transcription. This discovery highlights hormone receptor roles in neoplastic transformation.
Area of Science:
- Molecular biology
- Oncology
- Endocrinology
Context:
- Avian leukemia retroviruses carry the viral oncogene v-erbA.
- v-erbA is an altered form of the thyroid hormone T3 nuclear receptor.
- This oncogene plays a role in neoplastic transformation.
Purpose:
- To investigate the role of the viral oncogene v-erbA in neoplastic transformation.
- To understand how v-erbA affects cell differentiation and gene transcription.
- To explore the interaction of v-erbA with normal hormone receptors.
Summary:
- The viral oncogene v-erbA, derived from the thyroid hormone T3 receptor, promotes sarcoma transformation and blocks erythrocyte progenitor cell differentiation.
- The v-erbA protein acts as an antagonist to normal T3 and retinoic acid receptors.
- It alters the transcription of genes regulated by intact receptors, impacting cell differentiation and proliferation.
Impact:
- Demonstrates direct involvement of hormone receptors in cancer development.
- Provides insights into mechanisms of oncogenesis driven by altered nuclear receptors.
- Identifies potential therapeutic targets for hormone-dependent cancers.