cancer biology Flashcards
(28 cards)
what can you see when you look at cancer tumour
-different layers of cells
how does cancer occur
-disease of aberrant cell proliferation & differentiation
cancer incidences in the west
-high levels of cancers in oral cavity and pharynx, digestive organs, respiratory system, breast, reproductive tract, urinary system, blood and skin melanoma
-lower levels in nervous system, endocrine and thyroid system, bones
cancer incidences across the world
-lots of Japanese -> Hawaii migration showing cases in Japan to hawaii
-they have low levels of prostate, colon and breast cancer, but high levels of colon cancer in Japan
-caucasians have much higher levels of prostate cancer and much lower levels of colon cancer
what are the environmental influences of cancer
-Infection
-Diet
-Noxious agents
how does infection cause cancer
-viruses integrate into the genome frequency
-Src= master regulator in signal pathway for cell adhesion and proliferation and mobility
-Scr stands for sarcoma
-Peyton Roux:
=chicken with sarcoma in breast muscle
=remove sarcoma and break up into small chunks of tissue
= grind up sarcoma with sand
=collect filtrate that has passed through the fine pore filter
=inject filtrate into young chicken
=observe sarcoma in injected chicken
-Cancer arises because the virus encodes a hyperactive form of a human tyrosine kinase gene
-other examples ;
=Nasopharyngeal carcinoma (caused by Epstein-Barr virus)
=Cervical carcinoma (caused by human papillomvirus)
=Kaposi’s sarcoma (caused by human herpesvirus 8)
=Helicobacter pylorii can turn into gastric carincoma
-viruses
how does diet lead to cancer
-Aspergillus oryzae (koji mold – rice , peanuts) leads to hepatocellular carcinoma
-diet, overweight, lack of exercise, alcohol
how does noxious substances lead to cancer
-Asbestos (naturally occurring silicate) leads to mesothelioma- Diffuse pleural
mesothelioma (fatal)
-uv and ionising radiation
-occupational carcinogens
what else can cause cancer except environmental factors
-genetics
-Retinoblastoma
-Li-Fraumeni Syndrome
-Wilm’s Tumour
-Gorlin’s Syndrome
-Breast Cancer Syndrome
-Familial adenomatous polyposis coli (FAP
what can cancer be a consequence of
-chromosomal changes
-CML for example
what underlies CML
-chromosomal translocation (swapping of genes)
-Fluorescent In Situ Hybridisation
Why does this chromosomal translocation have such a devastating effect
-Fusion of two genes:
=ABL (9q34)
=BCR (22q11)
-kinase (phosphorylates other things) and a target protein which is turned off and (the kinase) a positive regulator of cell growth
-When fused to BCR, it cannot switch itself off
-ADP->ATP
-target protein switched on-> constant proliferation
what an oncogene
-A gene with the potential to cause cancer by transforming cellular behaviour
how do oncogenes come about
-Oncogenes are genetically DOMINANT
-arise from normal genes in cells regulating proliferation
-proto-oncogene ->
=deletion point mutation in coding sequence-> hyperactive protein made in normal amounts
=regulatory mutation -> normal protein greatly overproduced
=gene amplification-> normal protein greatly overproduced
=chromosome rearrangement-> nearby regulatory DNA sequences causes normal protein to be overproduced OR fusion to acovly transcribed genes produces hyperactive fusion protein
what was the first human oncogene
-Ras
-binds to GTP
-the last phosphate that binds in GTP is very close to 2 AA - glycine 12 and glutamine 51
whats Ras
- a protein called Sos that exists in 2 conformational shapes
-depedening whether it binds GTP or GDP
-when its bound to GTP its on, off for GDP
-a proto-oncogene
how can you change Ras from being off-> on
-nucleotide exchange
-another protein goes to approach Raw, reaches in a grasp GDP and pulls it out of the protein
-bc there’s lots of GTP floating around in cell, GTP then binds, and its switched on
-extrinsic
how does Ras get turned off
-Ras is an enzyme
-catalyse hydrolysis of GTP-> GDP to turn Ras off
-Ras isn’t good at doing this toug- bad enzyme
-intrinsic
whats The importance of ras in growth factor-induced growth
-EC queues to IC effects
-receptor tyrosine kinase in plasma membrane
-growth factor binds to receptor in tyrosine kinase causing them to dimerise
how does Ras get turned into an oncogene
-if mutation occur in the 2 AA, then there is an abolishment of GTPase activity meaning Ras can’t turn off ever
hypothesis for cell fusion experiment
-Normal cells express tumour suppressor genes that are lost during oncogenesis
-says hybrid cells are non-tumerogenic
Might tumour suppressor genes exist
yes- loss of growth suppressor gene more likely than gain-of-function oncogene mutations
no- loss of both alleles of putative growth suppressor genes unlikely
whats Retinoblastoma
-arises sporadically as well as in families
-usually only affects one eye- unilateral
Knudsen’s one/two-hit hypothesis: why was it important
provides evidence that:
- for tumour suppressor gene hypothesis
-that cancer requires loss of both wild-type alleles
-for the basis of inherited predisposition to cancer
