Cell Biology, Cancer

8/6/2019 Cell Biology, Cancer

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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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Cell Biology, Cancer