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Oncogenes: past, present and future
1Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Abstract:
1. Certain retroviruses contain specific genes (oncogenes) which induce tumours. 2. These viral genes were shown to have normal counterparts in the mammalian genome which were termed proto-oncogenes or cellular oncogenes. 3. This breakthrough provided a molecular explanation for tumour formation; viz. cells become transformed when regulation of cellular oncogenes goes awry. 4. Evidence for aberrant control of proto-oncogenes in human malignancies was obtained when chromosomal translocations in Burkitt's lymphomas and chronic myelogenous leukaemia localized to the myc and abl cellular oncogenes, respectively. 5. Recent studies have demonstrated that proto-oncogenes govern cellular proliferation and can be from any part of the signal transduction pathway, for example, growth factors, receptors, intracellular second messengers or nuclear transcription regulators.
Insights
Retroviruses can cause tumors by activating oncogenes. Proto-oncogenes, the normal versions in mammals, can lead to cancer when their regulation is disrupted, particularly in specific leukemias and lymphomas.
Area of Science:
- Oncogenomics
- Molecular Biology
- Cancer Research
Background:
- Retroviruses possess specific genes, known as oncogenes, capable of inducing tumor formation.
- Viral oncogenes have homologous counterparts in the mammalian genome, termed proto-oncogenes or cellular oncogenes.
- The dysregulation of cellular oncogenes provides a molecular basis for tumor development.
Purpose of the Study:
- To explain the molecular mechanisms of tumor formation.
- To investigate the role of proto-oncogenes in human malignancies.
- To understand how proto-oncogenes regulate cellular proliferation.
Main Methods:
- Comparative genomic analysis of viral and mammalian genes.
- Identification of proto-oncogene counterparts to viral oncogenes.
- Analysis of chromosomal translocations in human cancers (Burkitt's lymphoma, chronic myelogenous leukemia).
Main Results:
- Discovery of proto-oncogenes as normal cellular genes with counterparts in oncogenic retroviruses.
- Demonstration that chromosomal translocations in Burkitt's lymphomas and chronic myelogenous leukemia involve the myc and abl proto-oncogenes, respectively.
- Identification of proto-oncogenes as key regulators of cellular proliferation across the signal transduction pathway.
Conclusions:
- Aberrant regulation of proto-oncogenes is a critical factor in the development of human malignancies.
- Proto-oncogenes are integral components of cellular signaling pathways, including growth factors, receptors, and transcription regulators.
- Understanding proto-oncogene function is crucial for elucidating cancer development and progression.