Related Experiment Videos
Retroviral and human cellular oncogenes
Abstract:
Unexpected meeting of two separate lines of research resulted in the discovery of oncogenes. Oncogenes are deoxyribonucleic acid (DNA) sequences coding for polypeptide gene products which cause, or contribute to, neoplastic growth of cells. Oncogenes remain almost unchanged through evolution: oncogenes and their gene products of avian, murine, feline, simian and human species show close homology. Retroviruses possess three genes encoding virion structural proteins and envelope. The DNA copy of the viral genome (the provirus) recombines with DNA sequences of the host cell genome and thus acquires an additional DNA sequence of host origin (transduction). The newly acquired DNA sequences render the retrovirus oncogenic. Certain genomic DNA sequences extracted from human tumor cells induce malignant transformation in selected assay systems (transfection). The transforming genes of retroviruses show close homology to these cellular oncogenes. Retroviruses appear to have acquired cellular proto-oncogenes during past interactions with their host cells. In the cell, proto-oncogenes are presumed to fulfill fundamental functions of cell differentiation and mitosis. This is deduced from their preservation during evolution, i.e., proto-oncogenes of avian, lower and higher mammalian and human species display close DNA sequence homology and thus their gene products are also similar in distant species. When expressed in excess or in altered form or at a wrong chromosomal location or at an inappropriate time of the cell cycle, proto-oncogenes function as oncogenes by inducing mitoses and inhibiting differentiation of their host cells.
Insights
Oncogenes, DNA sequences driving cell proliferation, were discovered through research convergence. These genes, crucial for cell growth, are conserved across species and can arise from proto-oncogenes.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Oncogenes are DNA sequences encoding proteins that promote neoplastic cell growth.
- These genes are highly conserved across diverse species, indicating fundamental biological roles.
- Retroviruses can acquire host cell DNA sequences, becoming oncogenic.
Purpose of the Study:
- To explain the origin and function of oncogenes.
- To investigate the relationship between retroviral and cellular oncogenes.
- To understand the role of proto-oncogenes in normal cellular processes.
Main Methods:
- Comparative sequence homology analysis of oncogenes and proto-oncogenes across species.
- Transfection assays using DNA from human tumor cells to induce malignant transformation.
- Retroviral transduction mechanisms involving acquisition of host cell DNA.
Main Results:
- Oncogenes and their products show remarkable evolutionary conservation.
- Retroviruses can acquire proto-oncogenes from host cells, leading to oncogenesis.
- Human tumor DNA contains transforming genes homologous to retroviral oncogenes.
- Proto-oncogenes normally regulate cell differentiation and mitosis.
Conclusions:
- Oncogenes arise from proto-oncogenes, which have essential roles in cell division and differentiation.
- Aberrant expression or alteration of proto-oncogenes can lead to cancer.
- The discovery highlights the link between viral and cellular mechanisms in cancer development.