Oncogene definition
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Understanding Oncogenes: Definition and Role in Cancer
What is an Oncogene?
An oncogene is a mutated or overexpressed version of a normal gene, known as a proto-oncogene, that drives the transformation of a normal cell into a cancerous one. Proto-oncogenes are essential for normal cell growth and differentiation, but when altered by mutations, amplifications, or rearrangements, they become oncogenes that can lead to uncontrolled cell proliferation and cancer .
Mechanisms of Oncogene Activation
Mutation and Overexpression
Oncogenes can arise through various mechanisms, including point mutations, gene amplifications, and chromosomal translocations. These alterations result in either a quantitative increase in the gene product or a qualitative change in its function, leading to the deregulation of normal cellular processes . For instance, mutations in the Isocitrate dehydrogenase (IDH1 and IDH2) genes are early drivers in glioma and acute myeloid leukemia (AML).
Viral Integration
Some oncogenes are activated by viral infections. Retroviruses can insert their genetic material into the host genome, leading to the activation of proto-oncogenes. This process can result in the production of oncoproteins that disrupt normal cellular signaling pathways, contributing to tumorigenesis .
Functional Impact of Oncogenes
Deregulation of Cell Proliferation and Apoptosis
Oncogenes play a critical role in cancer by promoting cell proliferation and inhibiting apoptosis. They achieve this by subverting normal signal transduction pathways at various cellular levels, including the cell surface, cytosol, and nucleus. For example, tyrosine kinases like EGFR and PDGFR, and serine-threonine kinases like Raf and Akt, are well-characterized oncogenes that lead to increased cell proliferation and survival.
Cancer Stem Cells and Lineage Restriction
The cancer stem cell theory suggests that cancers originate from tissue-specific stem cells that have undergone transformation. Oncogenes can disrupt the normal homeostatic processes of these stem cells, leading to their restriction to a single cell lineage and contributing to the hierarchical nature of cancer.
Expanding the Definition of Oncogenes
Recent research has broadened the concept of oncogenes to include genes involved in metabolic processes, mitochondrial function, and even muscle contraction. For instance, mutations in mitochondrial respiratory chain complexes can prevent apoptosis and contribute to cancer progression. Additionally, proteins like the myocyte enhancer transcription factor 2 (Mef2) have been implicated in oncogenic transformation and metastasis.
Conclusion
Oncogenes are crucial players in the development and progression of cancer. They originate from normal proto-oncogenes that become dysregulated through various genetic alterations. Understanding the mechanisms by which oncogenes drive cancer can provide valuable insights into potential therapeutic targets and strategies for cancer treatment.
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