Genes involved in carcinogenesis there are four classes of genes can be affected to produce a neoplasm





  Oncogenes which means normal cellular genes that contribute to cancer when abnormal are called oncogenes .the normal counterpart of such a gene is called Proto-oncogenes which they are normal genes involved in cell division ,oncogenes are usually designated by three - letter abbreviations such as MYC or RAS .oncogenes are further designated by the prefix of (v-)for virus or (c-)for cell or chromosome
some. corresponding to the origin of the oncogene when it was first detected. Proto-oncogenes can be activated (have increased activity) or over expressed (expressed at increased protein levels) by translo­cation (e.g., abl). promoter insertion (e.g.c-myc), mutations (e.g . ras), or amplification (e.g .HER2/neu). More than 100 oncogenes have been identified

Oncogenes may be growth factors (e.g .. platelet-derived growth factor). growth factor receptors (e.g.. HER2/neu) intracellular signal transduction molecules (e.g. ras), nuclear transcription fac­tors (e.g. c-myc) or other molecules involved in the regulation of cell growth and proliferation. Growth factors are ubiquitous proteins that are produced and secreted by cells locally and that stimulate

cell proliferation by binding specific cell-surface receptors on the same cells (autocrine stimulation) or on neighboring cells (paracrine stimulation). Persistent over expression of growth factors can lead to uncontrolled auto stimulation and neoplastic transformation. Alternatively. growth factor receptors can be aberrantly activated (turned on) through mutations, or over expressed (continually pre­senting cells with growth-stimulatory signals. even in the absence of growth factors). leading cells to respond as if growth factor lev­els are altered. The growth-stimulating effect of growth factors and other mitogens is mediated through post receptor signal transduction molecules. These molecules mediate the passage of growth signals from the outside to the inside of the cell and then to the cell nucleus. initiating the cell cycle and DNA transcription. Aberrant activation or expression of cell-signaling molecules, cell-cycle molecules, or transcription factors may play all important role!in neoplastic trans­ formation. some examples of commonly mutated oncogenes include  Ras oncogenes(over expression of growth factor p21) ERB1andERB2(over expression of growth factors) Telomerase(important for cellular immortality  for examples

  • ras
The ras family of genes encodes small GTP-binding proteins that regulate several cellular processes. The H- and K-ras genes were first identified as the cellular counterparts of the oncogenes of the Harvey and Kirsten rat sarcoma viruses, while N-ras was isolated from a neuroblastoma. The N-. H-, and K-ras genes are located on chromosomes 1, 11, and 12. respectively. and encode for 21-kDa proteins that are nearly identical in amino acid sequence ,this genes promote malignant transformation by increasing proliferation
  • c-myc the c-myc proto-oncogenes encoding the c myc nuclear transcription factor was first identified as the cellular homologue of viral oncogenes (v-myc)of avian retrovirus the myc genes is located on the region of chromosome 8 that is translocated in burkitt,s lymphoma elevated or deregulated expression of c-myc has been detected in a wide range of tumours including breast colon cervical and small lung carcinoma osteosarcoma melanomas glioblastomas and myeloid leukemias
  • HER2\neu also known as c-erbB-2 is a member of the epidermal growth factor (EGF)receptor (EGFR)family and is one of the characterized tyrosine kinase this gene are rare in human cancer is frequently amplified and protein over expressed on many cancer including breast ovarian lung gastric and oral cancers
Tumour suppressor genes anti-oncogens

These are normal genes that tell cells when not to divide , they are down regulated by mutations , they tend to act in a recessive manner usually the malignant phenotype is expressed only when both copies are damaged or missing
  • P53 mutated in up to 50 % of tumours
 Antiapoptotic genes
  • Normal tissues are subject to genes regulating programmed cell death (apoptosis) neoplasm is associated with changes in cell senscence and immortalisation of the cell line eg loss of these normal controls resulting in a reduction in cell death this occurs when the genes controlling apoptosis are down regulated by mutation 
  • commonly affected apoptosis genes include bcl-2 inhibts apoptosis
DNA mismatch repair genes after normal cellular replication these are genes responsible for -4 recognizing and excising mutated genes segments if the genes themselves undergo mutation they become down regulated allowing accumulation of mutations within the cell
  • commonly affected DNA repair genes include MSH-2 there is also level of interaction between all these genes products exemplified by the role of p53 this protein is up regulated by cellular and DNA damage and high levels can be identified in damaged cells

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