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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