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Answer 1

Proto-oncogene: normal gene than controls cell growth, division, differentiation

Oncogenes: a mutatied in cancer/tumours:

Abnormally expressed

over expressed abnormally active (cMyk)

Proto-oncogenes -> oncogenes

1. mutation in coding sequence deletion
2. Gene amplification
3. Chromosomal translocation
4. Insertional mutagenesis

Egf growth factor binds to receptor (tyrosine kinase)

ligant needs to dimerise to cause dimerisation of receptors

each binds to each receptor - dimerize - autophosphorilates - and ready to phosphorylate other things - adaptor poriten (GRP 2) binds to SOS SH3 - SH2- SH3

SOS is important because it will cause phosphorylation to everything else

SOS phosphorylate Ras and activates it to Ras*

raf (mapkkk) - Mek (mapkk) - ERK (=mapk)

activates MAPK

Ras is dephosphoryalted by GTPase activating protein

IF ras is mutant blocks gap and then ras keeps going and is being overexpressed (too many protein production)

Ras goes through steps and activates IP3 kinase which phosphorylates PiP2 to PIP3 which makes PDK1 which makes PKB act and leads to growth

PTEN has the ability to stop growth, but if cells is in stress - regulates growth

If PTEN becames mutant - priblems

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APC genes - function: degradates b-catenin cell cell adhesion junctions but if apc is mutant you get massive build up of catenin which if is high binds to LEF1 and this complex upregulates gene transcritpion -> leads to cancer

Each polip -> chance to develop cancer

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p53 itself is controlled by MDM 2 ehich stops p53 levels from being too high

p53 gets degradated by proteosomes

but sometimes it is activated which is bad

FEEDBACK LOOP

dna damage -> mdm 2 phosphorylated and inhibits the inhibition of P53 so p53 levels are high and activates pathways to fix the cell

Mild damage - DNA repair or stops cell growth or APOPTOSIS

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colon cancer

Normal epithelium

1. APC mutation

Hyperproliferative epithelium

2. K-ras mutation

Adenoma created

3. p53 mutation

CArcinoma

metatasis

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Gene is ACTIVE in a tumour

Translocations/ point mutations

Not inherited

DOminant at cell level as only 1 mutation needed -> oncogene