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Oncogenes

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19 views20 pages

Oncogenes

Uploaded by

erikemustermann67
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Oncogenes

Dr. Rafay-ur-Rehman
MBBS, M.Phil
Oncogenes
• Oncogenes and their role in carcinogenesis
• Mechanisms of activation of proto-oncogenes
• Mechanism of action of oncogenes
• Tumor suppressor genes
• Oncogenic viruses
• Important tumor markers and their clinical
significance(CEA,FTP,HCG,Calcitonin,Prostatic
acid phosphatase)
Oncogenes and their role in
carcinogenesis
• Oncogenes are derived from activation of normal
cellular genes- proto-oncogenes –encode growth
stimulating proteins.
• “An altered gene whose product acts in a
dominant manner to accelerate cell growth or cell
division”
Proto-oncogenes Tumor suppressor genes
Oncogenes inactivated
↑ growth rate

Cancer
Oncogenic viruses
• RNA Viruses- Viral RNA is transcribed into Viral
DNA(Provirus) by Reverse Transcriptase.
• Viral DNA is incorporated into the genome of host
cell
• Deregulation of cell cycle ,inhibition of apoptosis,
abnormalities of cell signaling pathways.
• RNA viruses often carry oncogenes in their genomes
DNA Viruses – Act by down regulating the expression
and/or function of suppressor gene P53 & RB and
their protein products
Mechanisms of activation of
oncogenes
Mechanism Explaination
1. Mutation e.g.,Point mutation of RAS oncogene-gene product
is GTPase , having less activity in tumor cells
resulting in stimulation of activity of adenylyl cyclase
2. Promotor Insertion of a viral promotor region near a gene
Insertion activates the gene
3. Enhancer Insertion of a viral enhancer region near a gene
insertion activates the gene
4. Chromosomal A piece of one chromosome is split off and joined to
Translocation another. E.g.,Burkitt lymphoma , Philadelphia
chromosome
5. Gene Abnormal multiplication of a gene occurs resulting
Amplification in many copies. Can occur with oncogenes and also
genes involved in tumor drug resistance
Oncogenic viruses
(15% of human cancers)
Virus Genome
1. Epstein –Barr virus DNA 1.Burkitt Lymphoma
2.Nasopharyngeal
cancer
3.B-cell Lymphoma
2. Hepatitis B DNA HCC
3. Hepatitis C RNA HCC
4. Human Herpes DNA Kaposi Sarcoma
virus Type I
5. Human papilloma virus DNA Cancer of Cervix
6. Human T-Cell RNA Adult T-Cell Leukemia
leukemia virus type I
Mechanism of action of Oncogenes
• Activated oncogenes encode for onco-proteins
which
1. Affect Cell- signaling pathways- where they act as
a growth factor , a growth factor receptor , a G-
protein or a down stream signaling molecule.
2. Act to alter transcription
3. Act to deregulate the cell cycle
4. Affect cell-cell interactions
5. Affect process of Apoptosis
Ways by which oncogenes work
Some polypeptide Growth Factors
Tumor suppressor genes
• “Produce protein products that normally
suppress cell growth or cell division”
• When such gene is altered by mutation, the
inhibitory effect of its product is lost or
diminished
• Increased cell growth or cell division results
Properties of a few imp. Oncogenes
and Tumor suppressor genes
Properties of a few imp. Oncogenes
and Tumor suppressor genes
Differences between oncogenes and
tumor suppressor genes
Important tumor biomarkers and
their clinical significance
• Many cancers are associated with abnormal
production of enzymes ,proteins and hormones
that can be measured in plasma or serum.
• Helpful in management of patients with cancer
• Used in following the effectiveness of
treatment and detecting early recurrences.
• Not specific for cancers ( PSA in prostatitis &
BPH,CEA in heavy smokers,U.C.,Cirrhosis)
• Not used primarily for diagnosis of cancers
Some useful Tumor biomarkers
measurable in blood

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