Oncogenes
Oncogenes
Oncogenes
Presented by,
Tina K.J.
2nd Sem MSc Biotechnology
CUSAT
CANCER
Monoclonal
Initial neoplastic change affects a single cell
Field origin
Carcinogen acts on large number of cells
producing field of potentially neoplastic
cells
Two-hit Hypothesis
1 ) Oncogenes and Tumor Suppresor
Genes
Proto-oncogenes
2) Viral Oncogene Hypothesis
DNA virus
Do not contain viral oncogenes
Concepts:
Neoplastic changes frequently occur in cells
Altered DNA result in production of neoantigens
& tumor-associated antigens
Immune response (cytotoxic) to neoantigens as
foreign antigens
Neoplastic cells escaping recognition and
destruction become clinical cancers
Types Of Oncogenes
Mutated OR Inactivated
SV40
Functions of Tumour Suppressor gene
1. Antagonize the action of
oncogene. (ex.PTEN which converts
PIPIII to PIPII because PIPIII will activate
Pl-3/AKT which will activate BCL-2 that
will inhibit apoptosis and induce cell
transformation)
PIPII
PTEN PIPIII
PI-3
AKT
BCL-2
P16
P
Cdk4/cyclin D
Rb Rb
Rb inactive
G1
G1 S
S
M G2 M G2
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
MDM2
An E3 ubiquitin ligase
Inactivates p53
Binds specifically to the
N-terminus and inhibits
transactivation function
Also activates p53 to
proteasomal
degradation
p16
56
3)Chromosomal Translocation
4)Local DNA Rearrangements
5)Insertional Mutagenesis
Autosomal dominant
inheritance
Penetrance ~80%
T C T A C
AGCTG
Normal
Microsatellite
instability
Addition of nucleotide
repeats
Epigenetic control of cancer
genes
Epigenetics:
Mechanisms of gene expression control that can be
passed from one cell to its offspring, that are not
reflected in changes in DNA sequence
Examples:
DNA methylation
Histone modification
Noncoding RNAs
DNA methylation
Examples:
p16
RASSF1/NORE1
Local regions of DNA,
usually in gene
promoters (CpG rich
regions) maintain C-
methylation during
DNA replication
DNA methyltransferase
DNA Methylation
Hormone
Antihormonal
Hormone-stimulated therapy
cell proliferation
Mutation acquisition,
Tumor progression Hormonally-responsive
Normal cell
cancer
PREVENTING CANCER
DO’S
DON’Ts
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