Oncogene

Oncogene: Definition, history, function and activation, classification, examples and important message.

1. ONCOGENE Md. Ashfaq Aziz ID: 1925486670 BBT-615 (Advanced Cell Biology) Department of Biochemistry and Microbiology North South University Bangladesh

2. Introduction Onco means Cancer Oncogene is a gene which in certain circumstances can transform a cell into a tumor cell. A Proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression Proto-oncogene “Mutation” Oncogene The resultant protein encoded by an oncogene is termed Oncoprotein

3. History The term “Oncogene" was coined in 1969 by George Todaro and Robert Heubner . The first confirmed Oncogene was discovered in 1970 and was termed src . In 1976 Drs. Dominique Stehelin , J. Michael and Harold E. Varmus of the University of California demonstrated that oncogenes were activated Proto-Oncogenes, found in many organisms including humans.

4. Functions Of Proto-oncogene Help to regulate Cell growth and differentiation Involved in Signal Transduction Involved in execution of Mitogenic Signals Proto-oncogene Oncogene Oncoprotein Induce cell division and proliferation pathway Inhibit cell death

5. Image of Uncontrolled Cell Growth

6. Activation The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation: A mutation within a proto-oncogene, or within a regulatory region (for example the promoter region), can cause a change in the protein structure. An increase in the amount of a certain protein A chromosomal Translocation(another type of Chromosome abnormality)

7. Mechanisms Of Oncogene Activation 1. Point Mutation H- ras [codon 12] Normal CGC Gly Bladder cancer CTC Val 2. Gene Amplification Double minutes HSRs Normal copy Multiple copies

8. Mechanisms Of Oncogene Activation 3. Gene Translocation Ex. Burkitt’s Lymphoma

9. Result Of Oncogenes Activation Over-production of growth factors Flooding of the cell with replication signal Uncontrolled stimulation in the intermediary pathways Cell growth by elevated levels of transcription factors Cancer

10. Classification Of Oncogene Secreted Growth Factors - c-sis, hst Cell Surface Receptors - erb B, fms, ret, trk, fes, fms Intracellular Transducers - c- src , c- abl , mst , ras DNA-binding Nuclear Proteins - myc , jun , fos Regulators of the Cell Cycle - bcl , bax , bad

11. Examples of Oncogenes: More Monsters due to Point Mutation Amino Acid Position Ras gene 12 59 61 Tumor c-ras (H,K,N) Gly Ala Gln Normal cells H- ras Gly Val Ala Ala Leu Gln Lung carcinoma Bladder carcinoma K-ras Cys Arg Val Ala Ala Ala Gln Gln Gln Lung carcinoma Lung carcinoma Colon carcinma N-ras Gly Gly Ala Ala Lys Arg Neuroblastoma Lung carcinoma

12. Examples of Oncogenes: More Monsters due to Gene Amplification Oncogene Amplification Source of tumor c- myc ~ 20-fold Leukemia and lung carcinoma N-myc 5-1000-fold Neuroblastoma Retinoblastoma L-myc 10-20-fold Small-cell lung cancer c-abl ~5-fold Chronic myeloid leukemia c-myb 5-10-fold Acute myeloid leukemia Colon carcinoma

13. Examples of Oncogenes: More Monsters due to Translocation Neoplasm Translocation Proto-oncogene Burkitt lymphoma t(8;14) 80% of cases t(8;22) 15% of cases t(2;8) 5% of cases c-myc 1 Chronic myelogenous leukemia t(9;22) 90-95% of cases bcr-abl 2 Acute lymphocytic leukemia t(9;22) 10-15% of cases Bcr-abl 2

14. It is easy to kill cancer, but the challenge is keeping the patients alive at the same time.

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