Oncogenes are genes that can transform normal cells into tumor cells, typically arising from mutations or increased expression of proto-oncogenes. Activation mechanisms include point mutations, gene amplification, and chromosomal translocations, leading to uncontrolled cell growth and various cancers. Examples of oncogenes include c-myc, h-ras, and bcr-abl, each associated with specific malignancies.

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-myc1
Chronic
myelogenous
leukemia
t(9;22) 90-95% of cases bcr-abl2
Acute lymphocytic
leukemia
t(9;22) 10-15% of cases Bcr-abl2

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

15. THANK YOU