Download Midterm

Midterm
-Chapter 4,11,12,13,14
-Material only covered during the class
- slide No 23-26 from lecture 12 will not be covered in the midterm
-10/24 (Mon), 4:00-6:00pm
창의관 311호
-Office hour : 10/22 from 10am to 12pm
생명과학과 (building E6-3, Rm 3207)
Midterm
Types of
Questions
No of
questions
Note
Point
s
Multiple
choices
40
(1pt/Q)
40
Fill in the
blank or T/F
10
(More than 1
blank /Q)
40
Only in English
Short answer
4
(2.5 pts/Q)
Terminologies should 10
be in English
Essay
2
(5 pts/Q)
Terminologies shoud
be in English
Total
56 questions
10
100
Chapter 14
Mutation, DNA repair, and Cancer
Causes of Cancers
- Genetic inheritance
e.g., BRCA1
- Exposure to external carcinogens
e.g., UV, burnt food, smoking
Carcinogens cause alterations in DNA sequences or structure
=> Affect expression of genes critical in maintaining normal cell growth
- Or in combination
Two classes of genes that can cause a cancer when mutated
Mutations that cause
Hyperactivation of oncogenes
Loss of functions of tumor suppressor genes
Uncontrolled cell growth
Tumor
Two classes of genes that can cause a cancer when mutated
Two classes of genes that can cause a cancer when mutated
How proto-oncogenes become oncogenes?
How proto-oncogenes become oncogenes?
1) Missense mutation
2) Gene amplification
3) Chromosomal translocations
How proto-oncogenes become oncogenes?
How proto-oncogenes become oncogenes?
4) Retroviral insertions

Viral DNA may insert into a host chromosome
=> a viral promoter and response elements are next to a proto-oncogene
=> the overexpression of the proto-oncogene
Two classes of genes that can cause a cancer when mutated
1) Onogenes
: Genes that have the potential to cause a cancer
2) Tumor suppressor genes
: Genes that protect a cell from forming a cancer
Tumor suppressor genes
1) Normal role
: to prevent cancerous growth
2) Encode proteins with one of two functions
A) Maintain the integrity of the genome by monitoring and/or
repairing alterations in the genome
e.g. Checkpoint proteins
Tumor suppressor genes
Checkpoint proteins : Check integrity of genome before cells progress to
the next step of cell cycle
If abnormally detected => stop the cell division
e.g., p53 :
DNA damage sensor
promote DNA repair,
prevent cell cycle progression
about 50% of all human cancers are
associated with defects in this gene
Tumor suppressor genes
1) Normal role
: to prevent cancerous growth
2) Encode proteins with one of two functions
A) Maintain the integrity of the genome by monitoring and/or
repairing alterations in the genome
e.g. Checkpoint proteins
B) Negative regulators or inhibitors of cell division without a proper
signal
e.g., Retinoblstoms (RB)
Tumor suppressor genes
Retinoblastoma
Retinoblastoma: Cancer in Retina (diagnosed at an avg of 18 months)
Retina
Tumor suppressor genes
•The mechanism of Rb in Normal celll
Transcription activator that promotes expression of proteins
Involved in DNA synthesis
Cell growth signal
Rb becomes phosphorylated
Late G1
Cell cycle
progression
Transcription of Enzymes for DNA synthesis
Tumor suppressor genes
Loss of Rb function
1)
Deletion
2)
Inactivating mutation
Transcription of Enzymes
for DNA synthesis
In the absence of signal
G1 to S
Tumor suppressor genes
•The mechanism of Rb mutation in Retinoblastoma
Loss of Rb function
One copy of Rb gene is lost
Remaining copy
(inherited)
Undergoes mutation
Tumor suppressor genes
Loss of tumor-suppressor gene function

3 common ways

Mutation to inactivate its function

loss Chromosome that carries one or more tumor-suppressor genes

Abnormal methylation of CpG islands near promoter regions
cause compaction of chromatin => repress expression of tumor
suppressor
19
Cancer progression
Hyperactivation of oncogenes
Loss of functions of tumor suppressor genes
•Uncontrolled cell growth
Tumor
Genetic/epigenetic changes
Metastasis
(spread to other organs)
Accounts for over 90% of cancer related-death
The Hallmarks of Cancer
- Genetic inheritance
- Exposure to external carcinogens
Functional gain of Oncogenes
Functional loss of Tumor suppressor genes
Tumor cells
Normal cells
Tight control
Tumor cells
The Hallmarks of Cancer
External carcinogens
Genetic inheritance
Deregulation of
signaling pathways
Cancer cell
Common
phenotypic
traits
The
Hallmarks
of Cancer
Evading
XIAP
apoptosis
Sustained
angiogenesis
Self-sufficiency
FoxO1
In growth signal
MDM2
AKT
PI3K
Tissue invasion
& metastasis
Survival/
Survival/
Proliferation
Proliferation
Insensitivity to antiGrowth signals
Limitless
replicative
potential
Modified from Luo et al
Cell (2009) 136, 823-837
The Hallmarks of Cancer
Sustained Angiogenesis
Angiogenesis process
The Hallmarks of Cancer
Sustained Angiogenesis
Angiogenesis in tumor
Xenograft
Implantation of human colorectal
Cancer cells in to the skin of mouse
The Hallmarks of Cancer
Sustained Angiogenesis
VEGF mediated signaling pathways
VEGF
VEGFR-2
Vascular Endothelial cell
plasma membrane
Binding of L
Dimerization
Subsequent
signal transduction
Angiogenesis
The Hallmarks of Cancer
Sustained Angiogenesis
The role of VEGF in angiogenesis in tumor
Tumors treated with VEGFR inhibitor