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Carcinogenesis, Oncogenesis , or Tumorigenesis. It is the formation of a cancer , whereby normal cells are transformed into cancer cells. Agents which can induce tumors are called carcinogens.
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It is the formation of a cancer, whereby normal cells are transformed into cancer cells. • Agents which can induce tumors are called carcinogens. • Carcinogenesis is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. • The genetic hypothesis of cancer indicates that the tumor mass results from the clonal expansion of a single genetically transformed or mutated cell.
This means that tumors are monoclonal; single mutated cell transmits its character to the next progeny of cells which divide and expand forming a mass.
Cancersand tumors are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.
Carcinogenesis is a gradual multi-step process resulting in accumulation of multiple genetic mutations that cause the phenotypic characteristic of malignancy (excessive growth, local invasiveness, and distant metastasis). • Over a period of time, many tumors become more aggressive and acquire greater malignant potential. • This accumulation of mutations and increasing malignancy is referred to as tumor progression.
Genes regulating normal cell growth: • There are 4 classes of regulatory genes: • Proto-oncogenes: normal growth promoting genes. • Anti-oncogenes: growth inhibiting or growth suppressor genes. • Apoptosis regulatory genes: control the programmed cell death. • DNA repair genes: regulate the repair of DNA damage that has occurred during mitosis and also control the damage that has occurred to the other three classes of genes.
Oncogenes: • They are genes whose products (onco-proteins) are associated with neoplastic transformation. • Change of proto-oncogene into oncogenes may occur as follows: • Point mutation: alteration of a single base in the DNA chain e.g., e.g., RAS oncogene in colon, lung and pancreatic cancer.
Chromosomal translocations: It is transferee of a portion of one chromosome carrying proto-oncogene to another chromosome and making it independent of growth controls e.g., Philadelphia chromosome in chronic myeloid leukemia (t9;22), and c-MYC in Burkett's lymphoma.
Gene amplification: It is increasing the number of copies of DNA sequence in proto-oncogene. • This leads to increased mRNA and/or over- expressed gene products causing autonomous and excessive cellular proliferation e.g. Her-2/neu in breast and ovarian cancer (Her 2/neu; human epidermal growth factor receptor type 2).
Properties of malignant cells are: • Excessive and autonomous growth (grows without need of stimulation, self sufficiency in growth signals). • Insensitivity to growth inhibitory signals (does not respond to growth inhibition-inactivation of tumor suppressor genes). • Escape cell death by apoptosis. • Avoid cellular aging (limitless replicative potential).
Continued perfusion of cancer (development sustained angiogenesis). • Ability to invade and metastasize. • DNA damage and repair system (genomic instability resulting from defects in DNA repair). • Cancer progression and heterogeneity; clonal aggressiveness. • Multistep molecular phenomena (multistep carcinogenesis). • Micro-RNAs in cancer.
