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Dbl expression driven by the neuron specific enolase promoter induces tumor formation in transgenic mice with a
G L Colucci-D'Amato1, G Santelli, A D'Alessio
1Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università Federico II di Napoli, Italy.
Abstract:
The dbl oncogene, generated by the truncation of the amino-terminal portion of the proto-oncogene sequence, encodes a guanine-nucleotide-releasing factor. The transforming activity of this oncogene has never been demonstrated in vivo or in vitro except in the NIH 3T3 mouse fibroblast cell line. The expression of the proto-dbl transcript is confined to tissues and tumors of neuroectodermal derivation. Therefore, to study the transforming activity of the dbl oncogene in vivo, we have generated transgenic mice that express this oncogene in neuroepithelial tissues. Mice carrying the dbl oncogene did not develop a tumor. Successively, to establish whether dbl interacts with the tumor suppressor gene p53 in tumorigenesis, we have used a p53 deficient mouse strain. The results reported here indicate that dbl is capable of causing tumor formation in vivo when its expression is driven in an appropriate cellular and genetic environment.
Insights
The dbl oncogene can cause tumors in vivo, but only within specific cellular and genetic contexts. Its interaction with the p53 tumor suppressor gene is crucial for tumor formation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The dbl oncogene, a truncated proto-oncogene, encodes a guanine-nucleotide-releasing factor.
- Its transforming activity was previously unproven in vivo, limited to NIH 3T3 cells.
- Proto-dbl expression is primarily in neuroectodermal tissues and tumors.
Purpose of the Study:
- To investigate the in vivo transforming activity of the dbl oncogene in neuroepithelial tissues.
- To determine if dbl interacts with the p53 tumor suppressor gene in tumorigenesis.
Main Methods:
- Generation of transgenic mice expressing the dbl oncogene in neuroepithelial tissues.
- Utilizing a p53-deficient mouse strain to study dbl and p53 interaction.
- Assessing tumor formation in vivo.
Main Results:
- Transgenic mice expressing the dbl oncogene alone did not develop tumors.
- Co-expression of dbl with a functional p53 pathway did not induce tumors.
- Tumor formation occurred when dbl was expressed in a p53-deficient genetic background.
Conclusions:
- The dbl oncogene requires a specific cellular and genetic environment to drive tumor formation in vivo.
- The absence of functional p53 is a critical factor enabling dbl-induced tumorigenesis.
- These findings highlight the context-dependent role of oncogenes in cancer development.