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cancer
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Cancer is the fundamental aberration incellular behaviour.
Cancer cells can multiply in the absence of
growth promoter factors required for
proliferation of normal cells and they are
resistant to signal that induce apoptosis
Cancer cells invade the surrounding tissues, a
process called metastasis
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They form blood vessels called angiogenesis
During cancer development a cell can become
a cancerous if the following properties in the
normal cell altered:
Self sufficiency in growth signals Insensitivity to antigrowth signals
evasion of apoptosis
sustained angiogenis
Limitless replicative potential
tissue invasion and metastasis
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Cancer usually originate in proliferatingcells
When mutations occur in non-dividing cells
such as neurons and muscle, they generally
do not induce cancer
Adult Stem cells can divide in human body
and mutation in them can easily give rise to
cancer .
Leukaemia is example of cancer arise from
the haematopoietic stem cell
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The morphology and growth properties of the cancer
cells are different from their normal counterpart cells.
The mutations in the genome cause these differences.
Specific mutations transform the normal cells into
cancerous cells.
3T3 fibroblast cells were transformed with the small
piece of DNA extracted from a human bladder cancer
cells.
It was remarkable to find a small piece of DNA withthis ability to transform a normal cell into a cancerous
cell
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The mutant gene of ras gene which has a single mutation.
Normal Ras protein participate in the intracellular
signalling pathway
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However, most cancers arise from themultiple mutation in the cell. Multiple-hit
model proposes that multiple mutations are
often needed to cause cancer. .
DNA microarray analysis can reveal
differences in gene expression between
normal and cancer cells
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A lti- it el f c cer i cti
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There are seven types of proteins that can
participate in controlling cell growth andproliferation
They can be classified as proto-oncogens promote
cell proliferation
Tumour suppressive genes inhibit cell proliferation
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Genetics basis of cancer
Proto-oncogenes:
Most of the proteins encoded by the proto-oncogenes
participitate in controlling cell growth and proliferation
and these proto-oncogenes involved in the proliferationand cell growth
Mutation in these genes can convert them into oncogenes
that cause can cause cancer (Gain of function mutation)
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There are at least four mechanism that can produce
oncogenes from the corresponding proto-oncogenes:
Point mutatiuon in a proto-oncogenes that results in
a hyperactive protein product
Chromosomal translocation that fuses two gens
together and produce a hybride protein who is more
active than the normal proto-oncogens.
Chromosomal translocation that bring a proto-oncogens under the control of a different promotor
that cause the high production of the proto-oncogens
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Amplification (abnormal amplification)ofDNA segment containing the proto-oncogens.
That leads to the over production of the
protcocogens.
Virus can also cause cancer. They can also
insert oncogens that can cause cancer
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Loss of function mutation in tumour suppressor
genes.
Tumour suppressor genes encode protein that result in
the inhibition of cell proliferation:
Proteins that regulates or inhibit progression through
the specific stage of the cell cycle (p16 and Rb)
Some receptor for secreted hormones that inhibit cell
proliferation (TGF, the hedgehog receptor)
Check control points that arrest the cell cycle if the
DNA is damaged (p53)
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In proto-oncogenes one mutation in one allele is
sufficient to give rise to cancer
While in Tumour-suppressive genes two alleles
should have mutation for cancer progression
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