Lecture 5: Cancer Flashcards
(70 cards)
1
Q
what are the kinds of cancer-critical genes
A
- proto-oncogenes/ oncogenes dominant
- tumor suppressor genes recessive
2
Q
what are proto-oncogenes/ oncogenes
A
- promote cell proliferation
- identified by gain-of-function mutations (increased or unregulated activity)
- is dominant (only need one mutated allele to see the effect)
3
Q
what are tumor suppressor genes
A
- inhibits cell proliferation
- identified by loss-of-function mutations
- recessive trait (do not see an effect unless both alleles are mutated)
- need to lose the function of both alleles of the cancer critical gene to drive the cell towards cancer
4
Q
what is an example of proto-oncogenes/ oncogenes
A
- activation of bcr-abl gene in CML
- Myc
5
Q
what is an example of tumor suppressor genes
A
loss of Rb function in retinoblastoma
6
Q
in what kind of mutation are more oncogenes produced
A
overactivity mutation (gain of function)
7
Q
true/false mutations in cancer critical genes cause cancer on its own
A
- false
- but it can lead it there
8
Q
true/false cancer critical genes have the sole purpose to cause cancer
A
- false
- they do have other roles in the cell cycle
9
Q
what is glioblastoma
A
brain cancer
10
Q
what is the most common oncogenic events in glioblastoma
A
epidermal growth factor receptor (EGFR) gene mutations and amplifications
11
Q
how do EGFR mutations lead to overactivity
A
- inactive state
- there is a transmembrane protein, with receptor domains inside and outside
- active only when it bind EGF
- binding of growth factor will trigger intracellular signalling
- regulatory extracellular region is deleted
- this makes the receptor always active, because there is no where for EGF to bind
- so the signals are constantly being sent
12
Q
what causes retinoblastoma
A
loss of Rb tumor repressor function
13
Q
what happens if a normal, healthy individual inactivates a good Rb genes
A
no tumor
14
Q
what happens if an individual with hereditary retinoblastoma inactivates a good Rb gene
A
they get a tumor
15
Q
what happens if an individual with nonhereditary retinoblastoma inactivates a good Rb gene
A
- the first time nothing
- the second time in that cell leads to tumor
16
Q
what happens to most people with hereditary retinoblastoma
A
most develop multiple tumors in both eyes
17
Q
what happens to most people without hereditary retinoblastoma
A
about 1 in 30 000 will develop one tumor in one eye
18
Q
what happens with retinoblastoma once the cells like both Rb genes
A
the cells will go to S phase even when they’re not supposed to
19
Q
what is the normal function of the Rb gene
A
to stop a cell from entering S phase
20
Q
true/false a single mutation is enough to cause cancer
A
- false
- its done by an accumulation of several mutations over time
21
Q
why is there a decrease in cancer after 90 years of age
A
your cells dont divide as quickly when you get older (decrease in cell proliferation)
22
Q
why is there a long incubation period for a cancer to develop
A
- due to the multiple changes/ mutations that need to occur within a cell before it becomes cancerous
- you smoke, you get mutation, you get cancer, you die….. not immediate
23
Q
how large of a lag is there between carcinogen and cancer development
A
10-20 year lag
24
Q
what causes cancer of the uterine cervix
A
some papillomaviruses
25
describe the structure of papillomaviruses
- a type of virus that have circular DNA, made up of about 8000 nucleotides
- This DNA usually stays inside the basal cells of the skin (the bottom layer of skin cells) in a small, separate form called a plasmid
- The plasmid copies itself along with the host cell’s DNA, so everything stays in sync
26
what normally happens with papillomaviruses in the uterine cervix
- The virus doesn’t cause much trouble
- It only starts to mess with the cell cycle when it's ready to make new viruses, usually in the upper layers of the skin.
- causes a benign growth or wart
27
what sometimes happens with papillomaviruses in the uterine cervix to cause issues
- Something goes wrong, and the virus's plasmid DNA gets accidentally inserted into the host cell’s chromosomes
- This changes how the viral genes work inside the basal cells
- These genes, especially the ones called E6 and E7, can mess with the normal control of cell division
- When this happens, the cells start dividing uncontrollably, which can lead to cancer
- causes malignant tumor
28
E6 and E7 are what
two papillomaviral proteins
29
what does E7 do
- "sequesters" Rb
- *remember Rb is a protein that binds to the proliferation factor E2F. this stops the cell from proliferating*
- by sequestering Rb, the proliferation factor E2F is free
- cyclin E will be transcribed, allowing entry to S phase
30
what does E6 do
- binds to p53
- *remember p53 provides a safety brake on cell proliferation, making p21 transcription happen, which inhibits the G1/S cyclin/cdk complexes*
- with p53 now not working, cyclin E can do its thing and can enter S phase
31
what does Gardasil HPV vaccine (Merck) use
- recombinant form of the major structural protein (L1) of the virus
- immunodominant protein that can form viral-like particles (VLPs)
32
what is ColonCancerCheck
- ontario program that screens individuals age 50+
- using fecal immunochemical test (FIT)
- they check for tiny amounts of blood in the stool
- test for antibodies for hemoglobin
- blood in the stool doesn't mean you have cancer, just means you might
33
**true/false** a positive FIT test means you have colon cancer
- false
- means you might, so you need to go for further testing
34
how did we identify genes linked to colorectal cancer
- screen the tumors for mutations in genes known and suspected to be involved in other cancers
- examine many different colorectal tumors to look for common genetic alterations-> large chromosomal deletions
- examine families w geneic predisposition to colorectal cancers *with familial adenomatous polyposis coli (FAP)*
35
what causes FAP
- due to the deletion or inactivation of *both alleles* of the APC gene on chromosome 5
- *note that APC gene is adenomatous polyposis coli gene, not APC/C we learnt earlier*
36
what does APC normally do
is an inhibitory component of the Wnt signaling process
37
what happens if APC is missing or nonfunctional
- an overgrowth of the colonic epithelium will occur
- polyps develop
38
what is a good way to keep track of FAP if you have a family history of it
frequent colonoscopies
39
what is the suggested typical sequence of genetic changes underlying the development of a colorectal carcinoma
40
mutations found in both polyps and malignant tumors are likely to occur _____ *(early/later)*
early
41
mutations found only in malignant tumors are likely to occur _____ *(early/later)*
later
42
**true/false** a loss of Apc activity is commonly found in cells in the development of colorectal carcinoma
true
43
what is the most feared and misunderstood aspect of cancer
metastasis of cancer cells *(when they travel from one part to another)*
44
how does metastasis of cancer cells happen
- the cells tend to be sticky and hold together, but they lose their adhesive proteins
- cross the basal lamina
- enter bloodstream of lymphatic system
- exit circulatory system
- establishment at new site
- induce angiogenesis *are able to induce blood vessels*
- growth of metastasized tumor
45
angiogenesis is controlled by factors released by what
the surrounding tissues
46
what happens when tissue lacks oxygen
- the lack of oxygen triggers the secretions of VEGF
- VEGF stimulates angiogenesis
47
what does VEGF do
stimulates endothelial cells to sprout, stimulating angiogenesis
48
what is VHL and what does it do
- is a ubiquitin ligase
- invovled in degredation of HIG
- acts as a tumor suppressor
49
what is HIF
- *hypoxia inducible factor*
- stimulates transcription of the gene encoding the vascular endothelial growth factor
50
how is a philidalphia chromosome formed
- Chromosome 9 and Chromosome 22 swap some pieces of DNA (this is called a "translocation")
- When they swap, two genes, called Bcr (on chromosome 22) and Abl (on chromosome 9), get stuck together in a way they shouldn’t be
- This new combination is called the Philadelphia chromosome.
51
what does Abl normally do
- encodes a protein tyrosine kinase
- which is involved in cell signaling
- activates the production of T-cells
52
what is the problem with philidalphia chromosomes
- When Bcr and Abl are stuck together, they create a fusion protein, which is like a new, broken protein
- This fusion makes the Abl part always “on” — so it keeps telling cells to keep growing and dividing all the time, without stopping
- The bone marrow cells start growing too much, creating too many blood cells, leading to leukemia
53
what does Bcr normally do
encodes a protein w serine/threonine kinase activity but function is unclear
54
which form of cancer has a protein found *only* in cancerous cells
chronic myelogenous leukemia
55
what makes Bcr-Abl fusion protein a good target for chemo
- its only present in cancerous cells,, cause its not a natural protein
- so you can target *only* it for chemo, without harming the other healthy cells
56
what is Imatinib (Gleevac)
a drug used to treat chronic myelogenous leukemia
57
how does imatinib (gleevac) work
- Bcr-Abl is a bad protein (created by the Philadelphia chromosome) that keeps telling cells to grow uncontrollably.
- Normally, Bcr-Abl uses a molecule called ATP to add a phosphate group to other proteins (this is like turning on a switch that makes the cell grow and survive). This process is called phosphorylation.
- Imatinib works by blocking this process. It fits into the part of Bcr-Abl that normally holds ATP, kind of like putting a stopper in a bottle. When imatinib is in place, ATP can't bind to Bcr-Abl, and the phosphorylation process can't happen.
58
what is compound STI571
- imatinib gleevec
- signal transduction inhibitor
59
how do normal cells handle ionizing radiation
- p53 is induced, causing cell cycle to arrest
- if damage is too extensive to repair, apoptosis happens and cell dies
- if damage can be repaired, it is repaired, and cell continues on
60
how do cancer cells handle ionizing radiation
- p53 is lacking cause its a cancer cell
- no cell cycle stopping
- cell division with damaged chromosomes
- cells either die or cause cancer
61
**true/false** the most frequent result of ionizing radiation in cancer cells is cancer
- **false**
- normally the cell dies
62
**true/false** the most frequent result of ionizing radiation in normal cells is apoptosis
- **false**
- normally the damage is repaired and cell divides like normal
63
what do drugs ending in **mab** normally mean
monoclonal antibody (protein)
64
what do drugs ending in **nib** normally mean
small molecular inhibitor (usually synthetic molecules <900 daltons)
65
what is the Ras-MAP-kinase signaling pathway
- a process inside cells that helps control things like cell growth and division
- this pathway is turned on when certain signals from outside the cell (like growth factors) bind to special proteins on the cell surface called receptor tyrosine kinases (RTKs), such as the EGF receptor
- Once the RTK is activated by a signal, it sets off a chain reaction inside the cell, leading to the activation of Ras, which then triggers the MAP kinase pathway, causing the cell to grow or divide
66
what happens when B-raf gets mutated into an oncoprotein
- problems with the Ras-MAP-kinase signaling pathway
- uncontrollable cell growth, often cancer
67
what did scientists do to stop B-raf mutations from messing with the Ras-MAP-kinase signaling pathway
developed B-Raf inhibitors that specifically target the mutated B-Raf protein, blocking its action and helping stop cancer growth
68
how can you prevent cancer
- removal and elimination of known carcinogens
- early detection and treatment
69
what are problems associated w current cancer treatments
- surgery to remove tumors **not practical in matastasized cancers**
- radiation and chemo are usually **toxic to normal cells**
- **development of resistance** to either a single or multiple anticancer drugs
- survival of single cancer cell can lead to **resurgence** of disease
70
