OncogenesA Presentation on
Prepared & Presented by
Tareq HasanID 141 1989 070
Submitted toDr. Ishtiaq Mahmud
MSc. In Biotechnology ProgrammeDepartment of Biochemistry &
MicrobiologyD
r. Jekyll
Mr. H
yde
Oncogenes: Mr. Hyde of Genes!
Has potential to cause “Cancer”Over-expressed form of “Dr. Jekyll Genes”Originated from Retrovirus
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Oncogenes=
Cancer Genes
J. Michael Bishop Harold Varmus
Winners of Nobel Prize 1989 in Medicine or Physiology for “The Discovery of the Cellular Origin of Retroviral Oncogenes”
Proto-oncogenes: Dr. Jekyll of Genes!
Encode for protein with important functions
Produces the Furious Fives
Encodes the cellular proteins
for –
Normal Cell Growth
Cellular Differentiation
Homologous to the retroviral oncogenes
Explains their Amplification
Can convert into “Oncogene”
By various ways
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Leads to Cancer
As gentle asDr. Jekyll
Functions of Proto-oncogenes:Producers of The Furious Fives!
Proto – oncogenes produces five types of proteins – “THE FURIOUS FIVES”
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I: Growth Factors I
II: Receptors for Growth Factors and Hormones II
III: Intracellular Signal TransducersIII
IV: Nuclear Transcription FactorsIV
V: Cell-Cycle Control ProteinsV
Functions of Proto-oncogenes:General Signalling Pathway
• The five classes of Proteins
• “THE FURIOUS FIVES”
• The first fours are involved in General Cell Signalling
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What “Activates” The Oncogenes
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Activation of Oncogenes:Ways of Unleashing the Monster
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Proto-oncogenes
Regulatory Regions
Proteins encoded by Proto-oncogenes
Performs Normal Functions
Proteins encoded with altered Structure & Function
1Point
Mutation
2 Gene Duplication
Overexpression
3 Chromosomal Translocation
Hybrid Protein;no longer in control
Result of Oncogenes Activation
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Overproduction of growth factors
Flooding of the cell with replication signals
Uncontrolled stimulation in the intermediary pathways
Cell growth by elevated levels of transcription factors
Cancer
Examples of Oncogenes: More Monsters due to Point Mutations
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amino acid position
Ras gene 12 59 61 Tumor
c-ras (H, K, N) Gly Ala Gln normal cells
H-ras Gly Ala Leu lung carcinomaVal Ala Gln bladder
carcinoma
K-ras Cys Ala Gln lung carcinomaArg Ala Gln lung carcinomaVal Ala Gln colon
carcinoma
N-ras Gly Ala Lys neuroblastomaGly Ala Arg lung carcinoma
Examples of Oncogenes: More Monsters due to Gene Amplification
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Oncogene Amplification Source of tumor
c-myc ~20-fold leukemia and lung carcinoma
N-myc 5-1,000-fold neuroblastomaretinoblastoma
L-myc 10-20-fold small-cell lung cancer
c-abl ~5-fold chronic myoloid leukemia
c-myb 5-10-fold acute myeloid leukemiacolon carcinoma
Examples of Oncogenes: More Monsters due to Translocation
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Neoplasm Translocation Proto-oncogene
Burkitt lymphoma t(8;14) 80% of cases c-myc1
t(8;22) 15% of cases t(2;8) 5% of cases
Chronic myelogenous t(9;22) 90-95% of cases bcr-abl2
leukemia
Acute lymphocytic t(9;22) 10-15% of cases bcr-abl2
Leukemia
1c-myc is translocated to the IgG locus, which results in its activated expression
2bcr-abl fusion protein is produced, which results in a constitutively active abl kinase
Thank You
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Oncogenes Product Targeted Treatment: Result of 40 years of Research
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