INTRODUCTION
A disease in which cells divide abnormally and destroy body tissues. Three classes of genes are responsible for the onset of cancer. First one is proto oncogene the normally promotes cell growth. After mutation proto-oncogene changes into oncogene whose products are excessively active in growth promotion. Second one is tumor suppressor gene it normally restrain growth. Third class of gene often linked to cancer called genome maintenance genes.
Cancer forming cells are called oncogenes and the cancer forming process is called oncogenesis or tumurogenesis. Most cancer arise after mutation by cancer-causing Chemicals known as carcinogens, or by errors in the DNA replication and repair. A tumor that does not grow indefinitely and doesn’t invade the healthy surrounding tissues extensively is benign. A tumor that continuously grows and becomes invasive is malignant tumor. Most cancer deaths are due to invasive, fast growing malignant tumors.
Malignant tumors are of two types carcinomas and sarcomas. Carcinoma derive from endoderm and ectoderm. Sarcomas derive from mesoderm.
PROPERTIES OF CANCER CELLS
- They show loss of growth control.
- They do self proliferation and are insensitive to anti proliferative extracellular signals.
- Does not undergo apoptosis.
- Formation of new blood vessels occurs (angiogenesis).
- They metastasize and are generally
- Mostly depends on anaerobic metabolism pathway such as glycolysis and fermentation to a much greater degree than their normal counterparts.
- They bind to laminin and fibronectin in connective tissue collagen or proteases and then invade.
Cancer cells acquire a drive to proliferate that does not require an external individual signal. They fail to sense signals that restrict cell division and they continue to live when they should die.
THE GENETIC BASIS OF CANCER OR ONCOGENES
Proto-oncogenes
- Normal function of genes- promote cell survival or proliferation.
- Example of gene products- Anti-apoptotic proteins, components of signalling and signal transduction pathways that result in proliferation, transcription factors.
- Effects of mutation- Gain of function mutation allow unregulated cell proliferation and survival.
- Genetic properties of mutant gene- Mutations are generically dominant.
- Origin of mutation- Arise by point mutation, chromosomal translocation, amplification.
Tumor-suppresor genes
- Normal function of genes- inhibit cell survival or proliferation.
- Example of gene products- apoptosis promoting protein, inhibitors of cells cycle progression, checkpoint pathway proteins that assess DNA/chromosomal damage, components of signaling pathway that restrain cell proliferation.
- Effects of mutation- loss of functions mutation allow unregulated cell proliferation and survival.
- Genetic properties of mutant gene- mutations are genetically recessive.
- Origin of mutations- arise by deletion, point mutation, methylation.
Genome maintenance gene
- Normal function of genes- repair or prevent DNA damage.
- Example of gene products- DNA repair enzyme.
- Effects of mutation- loss of function mutations allow mutations to accumulate.
- Genetic properties of mutant gene- mutations are genetically
- Origin of mutations- Arise by deletion, point mutation, methylation.
Gain-of-function mutations convert proto-oncogenes into oncogenes
An oncogene is any gene that encodes a protein able to transform cells in culture, usually in combination with other cell alterations, or to induce cancer in animals. Most of the oncogenes are derived from normal cellular genes that is proto-oncogenes who’s wild type product promote cell proliferation or other features important for cancer.
For example the RAS gene is a proto oncogene that encodes an intracellular signal transduction protein that promotes cell division, the mutant rasD gene derived from RAS is an oncogene whose encoded protein product provides and exclusive or uncontrolled proliferation promoting signal.
The gain-of-function mutations that convert proto-oncogenes to oncogenes are genetically dominant that is mutation in only one of the two alleles is sufficient for induction of cancer.
Loss of function mutation in tumor suppressor gene are oncogenic
Tumor suppressor genes generally encode proteins that in one way or another in Inhibit cell proliferation. Loss-of-function mutations in one or more of these proliferation inhibitory proteins contribute to the development of many cancers. Prominent among the classes of proteins encoded by tumor suppressor genes are these five:
- Intracellular proteins that regulate or inhibit entry into the cell cycle.
- Receptors for signal transducers for secreted hormones or developmental signals that inhibit cell proliferation (e.g., TGF-b)
- Checkpoint pathway proteins that arrest the cell cycle if DNA is damaged (e.g., p.53)
- Proteins that promote apoptosis.
- Enzymes that participate in DNA repair.
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