Cell Transformation (normal cells to cancerous cells)
Cell transformation is a process in which the addition of certain malignant characteristics in the cell due to alteration in genetic material.
- induced by chemicals, carcinogens, radiations, viruses.
- In 1901 Hugo de Vries first used the term mutation to describe the sudden heritable phenotypic changes in evening primrose.
- In 1904 T.H.Morgan reported white-eyed drosophila in the population of red-eyed flies.
- In 1928 H.J. Muller first use x-rays to induce mutation in the fruit fly.
How normal cells converted to cancerous cells (In VIVO)?
- UV radiation causes pyrimidine dimerization of DNA which causes deletion/ insertion of nucleotide i.e. genetic makeup changes
- It leads to conversion of proto-oncogenes (normal genes) to oncogenes
- These oncogenes produce some malicious products which cause blockage of UV specific endonuclease enzyme (repair enzymes).
- Due to which DNA cannot be repaired and it leads to the conversion of a normal cell to cancerous cells.
A. Point Mutation:
Changes in single nucleotide sequences of the gene. It affects the cell in two ways:
a. Either by blocking the p53 gene which is required for apoptosis. Then the cell will continue to divide
b. Or by the change of k-RAS gene to mutant KRAS.
- KRAS is a gene required for the production of growth-related K-RAS proteins when combining with miRNA.
- If KRAS remains hyperactive then this mutant Ras keeps signaling molecules ON, and cells continue to divide.
- It occurs in the case of Retinoblastoma (eye cancer)
- Retinoblastoma (Rb) is a protein that acts as a regulator in cell cycle control. Phosphorylation of Rb releases E2F that will be required for the production of other proteins that regulate the cell cycle.
- During mutation in Ch-18 then Rb mutated and transcriptional factor E2F remains active. As result cells continue to divide
C. Insertion/ With Viruses
- It occurs in case of Avian Leukosis Virus
- In it, the virus inserts its own gene between the normal gene
- Like there is a gene that is responsible for production of myc protein.
- The virus inserts its own gene within it and causes modification in it.
- Myc protein has two parts: regulator and activator region. The virus blocks the regulator region by inserting its gene due to which myc continuously produces and causes the cells to continue to divide.
- It occurs in case of Burkett’s lymphoma
- Ch-8 contains gene sequence for ‘myc’ protein which is the transcriptional factor. If ‘myc’ gene gets gain of function mutation then cells continue to divide. So Ch-8 contains tight regulator for it
- But when it is translocated to Ch-14 which has heavy IG chain then it continuously produced along with antibodies
- Due to which cell continuously divides.