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.

History

• 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)?

1. Radiations

• 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.

2. Mutation

 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.

B.Chromosomal mutation.

• It occurs in the case of Retinoblastoma (eye cancer)

What happens?

• 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.

D.Translocation

• 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.

References

1. https://www.nature.com/scitable/topicpage/cell-division-and-cancer-14046590/!
2. http://whoami.sciencemuseum.org.uk/whoami/findoutmore/yourbody/whatiscancer/whathappensincancer/howdohealthycellsbecomecancer
3. https://www.ncbi.nlm.nih.gov/books/NBK9963/
4. https://www.cancer.gov/about-cancer/understanding/what-is-cancer

Cell Transformation (normal cells to cancerous cells)