Exam 1 Flashcards
(81 cards)
1
Q
local cancer, not metastasizing, likely won’t metastasize, less problematic
A
benign
2
Q
starting to spread or already spread to another site in body, problematic, kills
A
malignant
3
Q
endoderm
A
epithelial
4
Q
mesoderm
A
connective tissues, muscles, WBC, RBC
5
Q
ectoderm
A
nervous, skin
6
Q
why do epithelial cells often become cancer?
A
replicate a lot
7
Q
cancer of epithelial cells that don’t secrete things
A
squamous cell carcinoma
8
Q
cancer of epithelial cells that do secrete things
A
adenocarcinoma
9
Q
tumor characteristics
A
progressive, monoclonal, and altered metabolism
10
Q
explain how tumors can be progressive
A
normal –> hyper or metaplastic –> dyplsatic –> neoplastic –> metastatic
11
Q
tissue with excessive number of cells
A
hyperplastic
12
Q
tissue with cells in the wrong place
A
metaplastic
13
Q
individual cells appear abnormal but basement membrane still intact
A
dysplastic
14
Q
what falls between dysplastic and neoplastic?
A
adenoma, polyp, papiloma
15
Q
invasive and cells spread
A
neoplastic
16
Q
cells move to a new tissue
A
metastatic
17
Q
monoclonal
A
single cells becomes cancerous and replicates into whole tumor
18
Q
describe the experiment that explained why cancer is monoclonal and not polyclonal
A
only 1 band showing that only 1 type of Ig was present (all cells genetically identical and making exact same proteins versus if polyclonal would have multiple Ig
19
Q
normal metabolism
A
glucose (anaerobic glycolysis) –>pyruvate (aerobic with O2)–> 36 ATP
20
Q
hypoxia and metabolism
A
low O2- glucose –> pyruvate –> lactate
21
Q
tumor metabolism
A
- not adequate blood supply
- hypoxic
- use a lot of glucose
22
Q
warburg effect
A
cancer cells limit themselves to glycolysis even when O2 abundant
23
Q
protooncogene
A
reg, normal gene has potential to turn into oncogene
24
Q
oncogene
A
gene/protein that causes/drives cancer and prolif
25
mechanisms to activate a protooncogene to oncogene
1) retrovirus
2) point mutations
3) copy # increase
4) chromosomal translocations
5) miRNA
26
tumor suppressor genes functions
1) inhibitor of cell cycle
2) activators of apoptosis
3) inhibitors of protooncogenes
27
tumor suppressor gene losing function
LOH
1) mitotic recombination
2) during DNA replication
3) chromosomal nondisjunction
4) deletion of portion of chromosome
28
growth factor
protein made/secreted by one cell to tell another to prolif/mitosis/rep
29
paracrine growth factor signaling
2 cells near neighbors
30
endocrine growth factor signaling
2 cells not near neighbors
31
autocrine growth factor signaling
one cell makes own GF, telling to prolif
32
How does GF act as oncoprotein?
autocrine signaling- one cell makes own GF, telling to prolif (epithelial cell expressing GF receptor and due to mutation, expresses ligand)
33
EGFR
tyrosine kinase that tells cells to prolif ONLY when it binds EGF
34
describe EGFR/EGF in normal cell
EGF binds to 2 copies of EGFR, forces EGFR to homodimerize and turn on kinase activity (alone, EGFR can't phosphorylate itself, but if close to another, can start phosphorylating)
35
autophosphorylation vs transphosphorylation
EGFR p EGFR but not itself so trans
36
ligand independent firing
even without EGF, EGFR can dimerize and turn on kinase activity through 5 mechanisms which result in losing ligand binding domain and locking into dimerization shape)
37
Why is having signaling evolutionarily favorable?
- regulation
- redundancy --> safety in having a lot of steps in case something goes wrong
- signal amplification
38
Ras signaling protogene to oncogene ex
mutations
- switch glycine to valine in Ras protein making Ras always on by abolishing GTPase fun
- miRNA mut, lose ability to reg Ras protein levels and inhibit Ras transcription (more Ras protein in cell)
- glycine to arginine making PI3K better at P PIP2
39
integrin signaling in normal cells
need 2 signals to prolif
1) GF signaling
2) integrin signaling
*gets survival signal by attaching to ECM, only prolif if ECM and GF present
40
ECM limits
number cells in body, attach or die
41
integrin signaling in cancer cells
anchorage independent growth so only need GF signaling
| *gets survival and prolif signals without ECM
42
when integrins bind to ECM...
integrins cluster at focal adhesions occur so FAK can do transphosphorylation
43
integrin signaling steps
1) integrin clustering at a focal adhesion
2) focal adhesion kinase (FAK) will transphosphorylate
3) P FAK can bind to GRB2/SOS
4) Ras gets phosphorylated and activated by GRB2/SOS
44
PI3K is what type of signal
anti-apoptotic
45
Jak/Stat is a signaling pathway for
circulating cells
46
proteins involved in Jak/Stat pathway
GF cytokines, transmembrane receptor, Jak, STAT
47
Jak proteins
class of kinases that bind to transmembrane receptors, transphosphorylate when dimerization happens, P transmembrane receptor
48
STAT proteins
bind to P transmembrane receptor, get P, dimerize, go to nucleus to turn on expression of genes for proliferation
49
Beta catenin is involved in
GF signaling and binding cadherin
50
Wnt
type of GF that uses Beta catenin to turn on prolif (APC tumor repressor)
51
APC mutation
out of control proliferation in colon
52
no APC present
transcription ON all the time
53
colon cancer
- shed epithelial cells.. need to be repopulated
- stem cells located in crypts of colon
- stromal cells secrete Wnt GF to drive prolif of stem cells
54
Beta catenin in colon cancer
B-catenin off, prolif off
55
what happens if Wnt is not present?
- Wnt doesn't bind frizzled receptor
- APC and friends bind P Beta catenin
- Beta catenin degraded and not acting as transcription factor
56
what happens if Wnt is present?
- Wnt binds frizzled receptor
- APC and friends bind frizzled
- Beta catenin enters nucleus and turns on transcription of genes for prolif
57
why is the cancer phenotype recessive?
need 2 mutated copies, multiple issues accumulate for normal to cancer
58
Rb is a
tumor suppressor gene associated with retinoblastoma
59
familial retinoblastoma
usually both eyes affected, multiple tumors, slightly younger avg age of onset
60
familial retinoblastoma genetics
at birth, one inherited mutated RB gene and one WT --> LOH --> disease
61
sporadic retinoblastoma
usually one eye
62
sporadic retinoblastoma genetics
at birth both WT --> random de novo mut --> LOH--> disease
63
LOH ways
1) mitotic recombination
2) during DNA replication
3) chromosomal nondisjunction
4) deletion of portion of chromosome
64
mitotic recombination
during mitosis, homologous chromosomes swap "homologous" genetic info
65
during DNA replication
sometimes DNA poly will "jump" from one homologous chromosome to another (part of mut copied into WT)
66
chromosomal nondisjunction
unequal pulling of chromosomes, possible for cell to get 2 mut copies of chromosomes
67
deletion of portion of chromosome
part of WT randomly deleted + mut ---> missing WT copy of gene + mut version (2 mut in end)
68
VHL
ubiquitin ligase, kidneys and blood vessels
69
pVHL
involved in sensing O2 levels
70
H1F1a
transcription factor, turns on VEGF exp if O2 levels low
71
VEGF
tells blood vessel cells to prolif
72
problems with VEGF and HIFIa
cancer mut in pVHL that causes more VEGF
73
normoxia conditions and HIFIa
-HIFIa gets hydroxyl groups added
-pVHL can bind to HIFIa with hydroxyl groups
-pVHL adds ubiquitin to HIFIa
HIFIa gets degraded
74
normal cell cycle
* end M to R- cell taking in signals from environment and using signals to decide prolif or not
* R to M, cell no longer pays attention to external signals (committed)
75
cancer cell cycle
prolif without proper signals
76
cyclin/CDK levels
CDK proteins stable and cyclin fluctuate
77
external signals (integrin/GF) control which cyclin
D
78
cyclin + CDK required for
kinase activity
79
cyclin/CDK are proteins related to
DNA rep and mitosis
- P of histones --> loosening chromatin structure for DNA rep
- P of DNA poly subunits --> need for DNA rep
- P nuclear mem proteins --> lead to destruction --> allow M
80
no Rb is like
hyper P Rb (not bound DNA, transcription of cell cycle genes)
81
HPV causes
cervical cancer
- E7 protein from HPV adds ubiquitin to Rb --> degrade
- cell will then transcribe its cell cycle genes
