1
Q
clonal origin of cancer
A
- Cancer develops from one cell that gains a mutation that allows it to survive, grow, and divide to form a tumor
- Progeny of this cell can gain additional mutations along the way to make it more successful
2
Q
how does the body prevent cancer formation every day?
A
- There are trillions of cells in the human body
- Every day many cells might experience mutations
- But these cells are usually eliminated by the body’s control systems
3
Q
why is screening for tumours important?
A
- Cancers exist for many cell divisions before the tumor is first detectable
- Physician-recommended cancer screening can detect cancers earlier
- Treatment can slow or stop tumor cell population growth
4
Q
Carcinoma
A
cancers developing from epithelial cells
5
Q
Sarcoma
A
cancers developing from connective tissue & muscle
6
Q
Leukemia
A
cancers developing from blood cells
7
Q
tumour
A
cells that survive, grow, and divide inappropriately
8
Q
cancer
A
malignant tumor with cells that have invaded the surrounding tissue
9
Q
three features of tumour cells
A
- acquisition of mutations
- increased cell survival/decreased cell death
- increased cell division
10
Q
two features of cancer cells
A
- changes to cell-cell adhesion
- can invade the basal laminate
11
Q
why is metastasis so problematic?
A
as it allows tumour cells to colonise additional tissues
12
Q
how many cancer cells survive to form metastases whilst travelling through the bloodstream?
A
fewer than 1 in 1000
13
Q
state the steps of metastasis
A
- Benign tumor forms
- Tumor invades surrounding tissue (becomes cancerous)
- Cells enter blood or lymph vessels
- Cells circulate
- Cells escape vessel into other tissues
- Cells grow and divide to form a metastatic (secondary) tumor
14
Q
why is the low survival rate of metastatic cancer not problematic for the cancer?
A
because only one cell needs to survive to then cause problems
15
Q
what two pathways are carried by most cancer cells
A
- increased cell division
- decreased apoptosis
- most tumours carry mutations affecting both pathways
16
Q
describe how changes in cell adhesion can promote tumor growth
A
- healthy tissues sometimes extrude cells (eg shedding of cells from epithelial lining
- when healthy cells leave their protective environment, they lose access to survival factors and undergo apoptosis
- tumor cells escape this apoptosis
- tumor cells may be extruded into the body, rather than the lumen, promoting metastasis
17
Q
how are tumour cells able to form an optimal survival environment?
A
tutors can recruit other cells to form a microenvironment
- cancer cells secrete proteins that signals to blood vessels to grow towards them, and stimulate cells to provide growth factors
18
Q
why are cancer cells so genetically unstable?
A
- some mutations promote genetic instability: they allow cancer cells to gain additional mutations quickly
- eg mutations in cell cycle checkpoints or DNA repair
19
Q
two types of genetic instability in cancers
A
large-scale rearrangements
point mutations
20
Q
how do mutagens cause mutations?
A
- cells have two DNA repair pathways to fix any errors in DNA replication
- exposure to mutagens increases the probability of mutations
21
Q
are all mutagens chemicals?
A
no; for example, UV rays, X rays
22
Q
are all chemicals mutagens?
A
the vast majority of chemicals are not mutagens
23
Q
what is aflatoxin B1 an example of?
A
some chemicals are harmless until they are ingested and metabolised by liver enzymes
24
Q
describe aflatoxin B1 action
A
- naturally produced by some fungi
- also in some unnatural sources like cigarettes
- aflatoxin B1 by itself is harmless
- in the liver, you have cytochrome P-450 enzymes (normally detoxify things)
- with aflatoxin B1, it creates aflatoxin-2,3-epoxide which is a very strong mutagens, causing mutations
25
how can we detect chemical mutants?
The Ames Test:
1. take a test compound (potential mutagen), culture of histidine-dependent salmonella, and homogenised liver extract (you need to test it with and without homogenised liver extract)
2. mix and plate on agar medium lacking histidine
3. incubate at 37 for 2 days
26
Ames test - mutagen mutagen
there are colonies of histidine-independent bacteria
27
Ames test - nonmutagen result
no colonies form
28
why does Ames test use trials with and without homogenised liver extract?
in your liver, you have cytochrome P450 enzymes. sometimes, they detoxify things, sometimes they make things worse.
29
cancer-critical genes fall into two major classes
1. oncogenes - overactivity mutation (gain of function)
2. tumor-suppressor genes - underactivity mutation (loss of function)
30
what is the normal version of an oncogene called?
a proto-oncogene
31
what is the role of proto-oncogenes?
genes that normally promote cell survival, growth, and division
32
describe mutated oncogenes
- mutated versions have increased activity in tumour cells
- mutations are dominant - only one copy of the gene needs to be mutated
33
describe 4 different mutations that can lead to oncogene over-activity
- deletion or point mutation in coding sequence
- regulatory mutation
- gene amplification
- chromosomal rearrangement
34
result of having deletion or point mutation in coding sequence
hyperactive protein made in normal amounts
35
result of having regulatory mutation
normal protein greatly overproduced
36
result of having gene amplification
normal protein greatly overproduced
37
result of having chromosome rearrangement
- nearby regulatory DNA sequence causes normal protein to be overproduced
or
- fusion to actively transcribed gene produces hyperactive fusion protein
38
what is a non-mutation change that can also lead to oncogene overactivity?
epigenetic modifications can increase oncogene expression
39
give an example of the result of having deletion in coding sequence
- deleting key amino acids in extracellular ligand-binding domain can produce a version that is always active
- eg survival factor receptors, growth factor receptors, mitogen receptors
40
give an example of the result of having point mutations in coding sequence
- a point mutation can disrupt the GTPase activity of Ras oncogene
- it cannot hydrolyse GTP, so the signaling pathway is always on
41
describe over expression or gene amplification of Myc
Myc oncogene transcription factor promotes cell cycle progression:
- increased G1-Cdk activity
- increased G1-Cdk expression
- increased E2F expression
- decreased Rb activity (increased phosphorylation)
42
give an example of how chromosomal rearrangements can create overactive proteins
- Abl is a tyrosine kinase involved in cell signaling
- a chromosomal rearrangement creates a fusion between Bcr-Abl called the Philadelphia chromosome (fusion of Bcr gene on chromosome 22 and Abl gene on chromosome 9)
- this removes the regulatory component of Abl, making it hyperactive
43
what is the typical function of tumour suppressor genes?
genes that normally act to repress cell survival, growth, and division
44
how are tumour suppressor genes different in cancer cells?
- usually underachieve or inactive in tumor cells
- mutations are recessive - both copies of the gene must be mutated to have a cancer-promoting effect
45
loss of Rb function - normal, healthy individual
no tumour
- occasional cell inactivates one of its two good Rb genes but this doesn't jibe an impact
46
loss of Rb function - nonhereditary retinoblastoma
- occasional cell inactivates one of its two good Rb genes
- occasional cell inactivates its only good Rb gene copy
- excessive cell proliferation leading to retinoblastoma
47
loss of Rb function - hereditary retinoblastoma
- inherited mutant Rb gene
- occasional cel inactivates its only good Rb gene copy
- excessive cell proliferation leading to retinoblastoma
48
result of nonhereditary retinoblastoma
only 1 in 30,000 normal people develop one tumor in one eye
49
result of hereditary retinoblastoma
most people with inherited mutation develop multiple tumours in both eyes
50
so what three things determine cancer susceptibility?
genetics, environment, plain probability
51
six examples of mutations that can lead to tumour suppressor gene inactivity
- aneuploidy causes chromosome loss
- mitotic recombination event
- gene conversion during mitotic recombination
- deletion
- point mutation
- epigenetic silencing
52
loss of p53 function
- p53 tumor suppressor is activated under many different stress conditions when the cell might be “in danger”
- p53 normally leads to cell-cycle arrest, senescence, or apoptosis
- Loss of p53 function allows cells to survive when they should not
53
what is required for cancer progression?
multiple mutations are required for cancer progression
54
cancer-critical genes converge on
several key pathways
55
what key pathways do cancer-critical genes converge on?
cell cycle, cell proliferation, and cell survival
56
example of cancer-critical gene involved in cell cycle
Rb: cell cycle entry
57
example of cancer-critical gene involved in cell proliferation
Ras: signaling cascade that drives cell growth
58
example of cancer-critical gene involved in cell survival
p53: tolerance to stress and DNA damage
59
Gleevec
- Gleevec specifically targets the Bcr-Abl kinase created by the Philadelphia chromosome rearrangement
- Gleevec stops the hyperactive oncogenic kinase by binding to the ATP-binding site, inactivating it
BIO230
flashcards
Decks in class (26)
# Cards
-
Lecture 163
-
Lecture 271
-
Lecture 368
-
Lecture 4.47
-
Lecture 555
-
Lecture 659
-
Lecture 1 - Membrane Trafficking45
-
Lecture 2 - Cytoskeletal Networks58
-
Lecture 3 - Cell Adhesion54
-
Lecture 4 - Tissue Morphogenesis50
-
Lecture 5 - Tissue Patterning50
-
Lecture 6 - Tissue Renewal & Stem Cells55
-
Lecture 7 - Concepts in Cell Signaling69
-
Lecture 8 - Signaling via Small Molecules40
-
Lecture 9 - Signaling via Protein Modifications41
-
Lecture 10 - The Cell Cycle40
-
Lecture 11 - Programmed Cell Death43
-
Lecture 12 - Cancer59
-
L1-L3: How are cells and tissues organised spatially?157
-
L4-L6: How do multicellular organisms develop?155
-
L7-L9: How do cells communicate with each other?150
-
l840
-
l941
-
l1040
-
l1143
-
1259
