Biology and the molecular biology of cancer II Flashcards
Aim-To try to understand the molecular mechanisms leading to cancer. Objectives: To identify common oncogenes To examine different classes of oncogenes. The link with specific types of cancer. The role of viruses in cancer.
what occurs in an overactivity mutation
a normal cell undergoes a single mutation event and creates an oncogene
this allows for the oncogene to promote cell transformation
what is an overactivity mutation
a gain of a function
what is a underactivity mutation
a loss of a function
what occurs in a under activity mutation
a normal cell undergoes a mutation event= inactivates tumour suppressor gene and this leads for no effect of mutation in one gene copy in the second mutation event it inactivates the second gene copy leading to elimination of the TSG promoting cell transformation
what is oncogenesis
The process of activation of proto-oncogenes to oncogenes can include retroviral integration , point mutations, insertion mutations, gene amplification, chromosomal translocation and/or protein-protein interactions.
what interactions can be involved in oncogenesis
retroviral integration point mutations insertion mutations gene amplification chromosomal translocation and or protein/protein interactions
what are photo oncogenes
group of genes that cause normal cells to become cancerous when they’re mutated
what nature are mutations in proto oncogenes
typically dominant
what is the mutated version of a proto oncogene
oncogene
what kind of proteins do protoncogenes encode
stimulate cell division
inhibit differentiation
halt cell death
what do oncogenes do
increased production of proteins so
increased cell division
decreased cell differentiation
inhibit cell deathxt
what are the ACS studies for the numbers of men getting cancer in their lifetime
1 out of every 2 men
what are the ACS studies for the numbers of women getting cancer in their lifetime
1 out of every 3 women
how many cancer genes are associated with germline( inherited) mutations
70
what is the mutation from protooncogene to oncogene
a dominant mutation
how many cancer genes are associated with somatic( spontaneous) mutations
342
what is contact inhibition
if normal cells are taken and placed on a petri dish they will continue growing until they touch other cells and will grow in a monolayer
who discovered the first tutor causing virus
Peyton Rous
who is Payton Rous and why is he important
he discovered the first tutor causing virus
what was the virus called that Payton discovered
Rous sarcoma virus
when was the Rous sarcoma virus discovered
early 20th century
what was Rous studying
the transmission of tumours in chickens, He found that he could induce tumour formation in a once-healthy chicken by injecting small pieces of a tumour taken from a cancer-prone chicken
what can we see histologically in cancer cells when growing on a petri dish
we lose the contact inhibition and the cells start growing on one another
what did Rous filter
extracts of chicken tumours through membranes which allowed the virus to pass through but not bacteria
what was allowed to pass through the membrane in Rous experiment
the virus but not the bacteria- this was also seen to induce tumour formation in healthy chickens
what was allowed to pass through the membrane in Rous’ experiment
the virus but not the bacteria- this was also seen to induce tumour formation in healthy chickens
what type of virus is Rous sarcoma virus
a retrovirus
what was later discovered about the rods sarcoma viral gene
it was a host gene which had been hijacked by a virus
what was the host cell protooncogene called
c-src
what was the rous sarcoma viral oncogene called
V-SRC
what is the c-src gene involved in
the positive regulation of cell growth and cell division
what functions can protooncogenes carry out
- Growth Factors
- Protein Kinases
- Membrane Associated G-Proteins
- Nuclear DNA-Binding/Transcription Factors
what are the role on oncogenes in cells
growth factor
protein kinases
receptors
transcription factor
what are vascular epithelium growth factors responsible for
formation of new blood vessels
what is one way can a growth factor can show mutation
much more overactive than previously
what is the difference of v-src and c-src in the body
the difference of their origin and the gene dosage- the gene dosage of v-src is much higher
what are protein kinases
they are associated with the receptors recognise the growth factor-
what are membrane associated g proteins
also from the family of signal transduction proteins which relay the signal from outside the cell to inside and changes gene expression
what is the signal transduction cascade
the signalling molecule from the outside of the cell binds to the receptor
leads to a cascade where intracellular affector region and secondary messengers involved which changes gene expression
what is one way of treating colorectal cancer
blocking the epidermal growth factor signal- block with an antibody and disrupt the signalling pathway
how do protein kinases work
protein which can attach a phosphate to another protein-intracellular cell transduction works
- the growth factor binds to the receptor
- receptor changes the 3D structure
- causes the relay of the phosphorylation signal passed by different protein to the nucleus where the change in gene transcription happens
what are protein kinases
protein which can attach a phosphate to another protein-intracellular cell transduction works
how can protein kinases become mutated to become oncogenes
by continuing to bind to the receptor and therefore the phosphorylation signal keeps on happening allowing for the change in gene transcription
how are cell activities and interactions tightly regulated
by cell signalling
what does disruption of cell signalling ultimately lead to
cancer
what does the c sis gene encode for
the PDGF beta chain
what does PDGF beta chain stand for
the platelet derived growth factor
where is the v sis gene found
in the simian sarcoma virus
give examples of growth factor oncogenes
c sis gene
v sis gene
int-2 gene
KGF/Hst gene
what does the int-2 gene encode for
FGF related growth factor
what does the KGF gene encode for
FGF related growth factor ( fibroblasts growth factor)
where was the KGF gene identified
in gastric carcinoma and Kaposis sarcoma cells
what does KGF Stand for
Keratinocyte growth factor
in which population is karposi’s sarcoma seen
in people which suffer from AIDS
what is important about the signalling pathways
they are all interconnected and we are still learning about them
what are RTK
receptor tyrosine kinases
how do receptor tyrosine kinases work
- the receptor binds to the growth factor
- kinase activity is stimulated and the tyrosine kinases move closer to one another
- tyrosines inside the cytosol are phosphorylated
- intracellular proteins bind to the phospho tyrosine docking sites
which type of mutations have been linked to lung and gastric cancer
ERBB2
what is erbb2
a specific receptor tyrosine kinase
how might cancer be caused
by the mutation in the FGFR( fibroblast growth factor receptor)
give example of a GTPase
RAS
WHAT IS RAF
a serine/threonine kinase
what is CDK4
cyclin dependant kinase
what is CDK4 associated with
breast cancer
myeloma
melanoma
what does CDK4 help with
control cell division
what happens when CDK4 is mutated
makes an abnormal protein which is too active and this makes cells divide abnormally fast which could lead to tumour formation
give examples of transcription factors
Myc gene
Fos gene
P53 gene
describe the Myc transcription factor gene
A disrupted human c- myc gene has been involved in haematopoietic neoplasias
where was Myc gene originally found
in avian myelocytomatosis virus
what does disruption of the c-myc gene cause
haemotopoietic neoplasms and has been linked to retroviral integration and transduction as well as chromosomal rearrangements
Where was the fos gene identified
In the feline osteosarcoma virus
What complex is formed with fos
A transcriptional regulatory complex- fos jun complex
What joins with fos to form the transcriptional regulatory complex
A second protooncogene called Jun
Where was p53 first identified
As a major nuclear antigen I’m transformed cells
What is the most identified mutant protein in human tumours
P53
what is the gene product of the p53 gene
a tumour supressor gene
how were tumour suppressor genes first identified
by making cell hybrids between tumour and normal cells
give examples of of tumour suppressor genes
retinoblastoma susceptibility gene (RB1),
Wilms’ tumours (WT1),
neurofibromatosis type-1 (NF1),
familial adenomatosis polyposis coli (APC or FAP), and those identified through loss of heterozygosity such as in colorectal carcinomas (called DCC for deleted in colon carcinoma)
p53 which was originally thought to be a proto-oncogene.
what is the function of p53 genes
to check if there is damage in the DNA and then if there is proteins are produced to repair that Damaged DNa
what has been associated with tumours of the lung colon and breast
the loss of heterozygosity in the short arm of chromosome 17 which includes p53 gene
what has seen to be lost in chromosome 17
the loss of heterozygosity in the short arm- this is where p53 is located
when we analysed murine leukemia cell lines what was shown
the p53 locus was lost by insertions or deletion of both alleles
what can p53 detect
senses DNA damage: hyperproliferative signals
dna damage
telemere shortening
hypoxia
describe p53
p53 is a protein that regulates cell division.
It prevents cells dividing too fast.
It also prevents cells dividing if there is DNA damage.
If the DNA damage cannot be repaired, p53 signals for apoptosis/cell death to be activated
what can p53 do when it detects a damage
cell cycle arrest
senescence- not killed but doesnt do much
apoptosis
what are cells exposed to
environmental carcinogens
what bacteria is linked to stomach cancer
helicobacter pylori
which parasite is linked to bladder cancer
SCHISTOSOMA HAEMATOBIUM
which parasite is linked to billary cancer
pancreatic cancer
and gallbadder cancer
Clonorchis sinensis AND
opisthorchis viverrini
what are the two distinct types of tumour viruses
DNA genomes papilloma and adenovirus
RNA genomes retrovirus
what are rna tumours common in
chickens
cats
mice
what is the known human retrovirus
human t cell leukemia virus and HIV
how does the transformation of DNA tumour viruses into cancer occur
by protein protein interaction
describe t antigens
- proteins encoded by the dna tumour viruses/ t antigens can interact with cellular proteins
- this moves away the cellular proteins from their nromal functions
how can oncogenesis by retrovirus occur
Retroviruses can carry viral versions of cellular proto-oncogenes (v-onc).
Contained within the sequences at the ends of the retroviral genome are powerful transcriptional promoter sequences termed long terminal repeats (LTRs). These can activate host genes near to the site of integration.
what virus is involved in stomach cancer
hodgkin and non hodgkin lymphomas and nasopharyngeal cancer
epstein barr virus
what virus is associated with hepatocellular carcinoma
hep b/C- causes liver inflammation
what virus is associated with karposi sarcoma and non hodgkin lymphoma
HIV
what virus is associated with cervical anogenital head neck and oral cancers
HPV- AKA an std
some strains are high risk strains
what cancer is associated with merkel cell polyomavirus
skin cancer
what cancer is associated with human t cell lymphotrophic virus type 1
t cell leukemia and lymphoma
how do people get oral cancer
HELP- the two pathways
The use of tobacco (smoking, snuff and chewing paan) and alcohol (beers, wines or spirits).
Exposure to the HPV-16 virus (human papilloma virus –type 16), a recently identified aetiology, and the same one which is responsible for the vast majority of cervical cancers in women.
how do 7% of people get oral cancer
from no currently identified tissue therefore have some genetic disposition
