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Mechanisms of Oncogenesis

  • Living reference work entry
  • First Online:
Handbook of Oncobiology: From Basic to Clinical Sciences

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Abstract

Carcinogenesis can be due to replication errors, faulty repair of damaged DNA, and exposure to DNA-damaging agents. The two major carcinogenesis mechanisms are activation of oncogene and inactivation of tumor suppressor gene. Among oncogenes are cell cycle regulators (bcl, barc), the secreted growth factors (c-sis, hst), cell surface receptors (erb B, fms, ret, trk, fes), intracellular transducers (c-src, c-abl, mst, ras), and DNA-binding nuclear proteins (myc, jun, fos). Oncogenes including E2F-1, beta-catenin, Myc, and Ras increase ARF levels. ATM and ARF control the function of MDM2, which is a negative regulator of tumor suppressor gene TP53 and RB1. Inactivation of TP53 is a frequent and early event in carcinogenesis. TP53 and RB1 play an important role in regulation of cell cycle, apoptosis, DNA repair, and suppression of tumor formation. The level of TP53 and MDM2 fluctuates in response to genotoxic stress signals, ribosomal stress, psychological stress signals, and oncogenic activation. Genotoxic stress signals including radiations cause DNA damage resulting in activation of ATM and ATR genes. DNA damage signaling and double strand break repair by homologous recombination, mRNA splicing, and microRNA biogenesis are influenced by BRCA1. The loss of function of BRCA1 and BRCA2 genes impairs DNA homologous recombination repair pathway and results in genetic instability and an increased risk of cancer, especially breast or ovarian. RAD51, a conserved eukaryotic gene, plays a major role in DNA repair during DSB and is also associated with modulation of HIF-dependent signaling pathways involved in promoting adaptation in cancer cells in hypoxic conditions. The HIF-α-c-Myc pathway influences cell–cell interaction, malignant progression, aggressive local invasion, and epithelial-mesenchymal transition. As tumor growth requires continuous angiogenesis, HIF-1α and HIF-2α induce angiogenesis by activation of expression of angiogenic pathway involving VEGF and VEGFRs. If DNA damage is unrepaired, viral integration can block DNA repair pathways or prevent recruitment of repair proteins like RAD51 to damage DNA site. The HPVE6 and E7 oncoproteins can bind to the tumor suppressor proteins p53 and RB1, inhibiting their function. Oncogenesis is the maintenance and evolution of cancer after its initiation. The mechanisms involved in oncogenesis can be viral integration in the genome or non-viral mechanisms of chromosomal aberration, gene amplification, and even modification at level of nucleosome and histones. Understanding these interactions has implications for future therapeutic regimes for cancer.

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Authors and Affiliations

  1. Department of Human Genetics, Guru Nanak Dev University, Amritsar, India

    Kamlesh Guleria & Vasudha Sambyal

Authors
  1. Kamlesh Guleria
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  2. Vasudha Sambyal
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Corresponding author

Correspondence to Vasudha Sambyal .

Editor information

Editors and Affiliations

  1. Dept. Biotechnology, Panjab University, Chandigarh, Chandigarh, India

    R. C. Sobti

  2. NCR Biotech Science Cluster, Translational Health Sci & Tech Inst, Faridabad, Haryana, India

    Nirmal K. Ganguly

  3. National Chair in Cancer Research, Rajiv Gandhi Center for Biotechnology, trivandrum, Kerala, India

    Rakesh Kumar

Section Editor information

  1. Department of Biotechnology, Panjab University, Chandigarh, India

    Ranbir Chander Sobti

  2. Swami Rama Himalayan University, Dehradun, Kerala, India

    Rakesh Kumar

  3. NCR Biotech Science Cluster, Translational Health Science and Technology Institute, Faridabad, India

    Nirmal K. Ganguly

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Guleria, K., Sambyal, V. (2023). Mechanisms of Oncogenesis. In: Sobti, R.C., Ganguly, N.K., Kumar, R. (eds) Handbook of Oncobiology: From Basic to Clinical Sciences. Springer, Singapore. https://doi.org/10.1007/978-981-99-2196-6_9-1

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  • DOI: https://doi.org/10.1007/978-981-99-2196-6_9-1

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  • Print ISBN: 978-981-99-2196-6

  • Online ISBN: 978-981-99-2196-6

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