Exam III: Lecture 10 Flashcards
Over __% of human cancers are caused by viruses
20
What are 5 common viruses that cause cancer?
- EBV
- HBV
- HCV
- HTLV I
- HPV
1 in 3 people will suffer from cancer
true
Cancer can be caused by a huge number of factors damaging the cell and when a critical number or hits have damaged the cell it can get ____
Transformed = cancer
How did scientist figure out that viruses can induce cancer?
1908 = discovered leukemia in chickens was infectious
1911 = a tumor in chicken caused by a virus. Can induce tumor formation in another chicken by injecting the sercoma of a cancerous chicken
Names Rous Sarcoma Virus
HBV; family, cancer type, cases/year
Hepatitis B Virus
Hepadnavirus
Hepatocellular (Liver) Cancer
340,000
HCV; family, cancer type, cases/year
Hepatitis C Virus
Flavivirus
Hepatocellular (Liver) Cancer
195,000
EBV: family, cancer type, cases/year
Epstien-Barr Virus
Herpesvirus
Burkitt’s, Hodgkin’s, Post transplantation lymphoma Nasopharyngeal carcinoma
113,400
HPV: family, cancer type, cases/year
Human papilloma virus
Papillomavavirus
Cervical cancer, anal cancer, penis cancer, head and neck carcinoma
561,180
HTLV I: family, cancer type, cases/year
Human T Lymphotrophic Virus
Retrovirus
Adult T cell leukemia
3,300
KSHV: family, cancer type, cases/year
Kaposi’s Sarcoma-associated herpes virus
Herpesvirus
Kaposi’s sarcoma, pleural effusion lymphoma
102,000
HBV: mechanism, oncogene, onc. function
Hepatitus B Virus
Chronic Inflammation
X protein
Molecular-signaling dysregulation inhibition of p53
HCV: mechanism, oncogene, onc. function
Hep C
Chronic inflammation
unknown
EBV: mechanism, oncogene, onc. function
Epstein-bar
Oncogenic
LMP-I
Molecular signaling dysregulation of NFkB activation lymphoproliferation
HPV: mechanism, oncogene, onc. function
Human Papaloma Virus
Oncogenic
E6, E7
Inhibition of p53 and Rb Cell adhesion dysregulation
HTLV I: mechanism, oncogene, onc. function
Human T Lymphotrophic Virus
Oncogenic
Tax
Molecular signaling dysregulation NFkB activation immortalization
KSHV: mechanism, oncogene, onc function
Kaposi’s Sarcoma-associated herpes virus
Oncogenic
8 differnent ones (vCyclin)
Cell cycle dysregulation, inhibition of apoptosis, immune evasion, autocrine and paracrine fucntions
Talk me through the regulation of the cell cycle from G1/S-cyclin to DNA synthesis
G1/S-cyclin > activates G1-Cdk (cyclin dependent kinase) > G1-Cdk phosphylated Rb protien = inactivating it > Active E2F ? S-phase gene trascnription > S-cyclin > Activates S-Cdk > DNA synthesis
Talk me through the regulation of the cell cycle from mitogen to the production of G1/S cyclin
Mitogen = growth factor binds to TKR (tyrosine kinase receptor) > activated Ras > MAP kinase cascade > activation of gene reculatory protein > immediate early gene expression > Myc = gene regulatory protein»_space;> G1/S cyclin
Is Ras an oncogene or a tumor supressor?
Oncogene
Is p53 an oncogene or a tumor suppressor?
Tumor Suppressor
What are 4 causes for p53 to be in stabilized and active?
- Hyperproliferative signals
- DNA damage
- Telomere shortening
- Hypoxia
What are 3 effects of p53 being stable and active?
- Cell cycle arrest
- Senescence
- Apoptosis
Talk me through the protection of the cell cycle from DNA damage to Inactivated G1/S /S-Cdk
DNA damage > ATM/ATR activation > Chk1/Chk2 kinase activation > phosphorylation of p53 > p53 is stable and active > p53 acts as a TF > produces p21 > p21 binds to Cdk and inhibits it
Viruses have devised a variety of ways to activate the cell cycle
true
Why is activating the cell cycle advantageous to the virus?
- Lead to cell death
2. Latent and persistant viruses often trigger transformation
Viruses interfere with the signal transduction pathways to _____ oncogenes or to ______ tumor suppressor genes (inactivate/activate)
Activate oncogenes
Inactivate tumor suppressor genes
Viruses can interfere with ______ pathways
Apoptotic
Viruses cause cell death in many organs they infect, this may lead to what?
The activation of cell division in an attempt to heal > expose the cell to a greater possibility of acquiring a transforming mutation
Activation of proteins involved in the cell cycle by the virus may predispose the cell to what?
continue cycling the cell in an uncontrolled manner leading to tumor formation
Tell me a story about Epstein-Barr virus
Denis Burkitt > described a cancer found in children in Uganda, East Afria = developed tumors in the jaw which grew rapidly and killed them in a manner of months > restricted to some villages but not other = Epstein said “this must be the work of a virus” > Epstian and barr biopsy the tumors and grow them in culture > found virus = EBV
How many people have Epstein-Barr infections?
90%
What was the eventual answer to why Burkitt’s lymphoma only appeared in some areas of Africa?
A chromosomal translocation which activated c-myc oncogene is required before the virus can transform the cell
The chomosomal translocation happened and some point and then the decendents spread through diffrenent parts of Africa
What is the very general mechanism of EBV?
EBV infects B cells and establishes a latent infection
A limited set of _______ are expressed with no production of _______ virus when EBV is latent
Viral Genes
Progeny virus
What genes are expressed during latency of EBV?
- EBNA
- EBER (EBV-encoded RNA)
- LMP
How does overexpression of c-myc predispose people to cancer?
B + T cells have increased rates of recombination > sometimes you get a strong enhancer infront of c-myc > overproduction of c-myc = oncogene > cancerous cell
What does EBNA-1 do?
binds to viral DNA and maintians it as an episome
What does LMP-1 do?
Inserts into the membrane of the B cell > acts as a mitogen receptor > stimulates cell division
What does EBNA, EBER, and LMP do as a whole?
Downregulate the expression of HLA-I and immunogenic EBV proteins
How does the downregulation of the expression of HLA-I and immunogenic EBV proteins help the virus?
It helps EBV evade the immune system
HLA-I presents viral peptides to T cells
Immunogenic EBV proteins = trigger the immune system
Nasopharylgeal carcinoma (NPC) is endemic in what population?
Southern Chinese
A strong association between NPC risk and ______ on chromosome ___ has been identified
HLA locus on chromosome 6p
How does NPC risk due to HLA locus on chromosome 6p relate to EBV?
There is a link between the presentation of EBV antigens to host immune cells and NPC risk
EBV infection in NPC is ____ in origin, suggesting that NPC develops from what?
Clonal origin
NPC develops from the clonal expansion of a single EBV-infected cell
HPV expresses what two key proteins when transforming?
E6 and E7
What does E7 do?
binds to Rb, p107, cyclin A, B-myb
What does E6 do?
Binds to p53 and induces its degradation
What does E5 do?
It is a part of BPV which binds to PDGF (growth factor) receptor > dimerization and activation
What two key proteins does adenovirus express during transformation?
E1A
E1B
What does E1A do?
Binds to cell cycle proteins such as Rb and p107
What does E1B do?
Binds to and inhibits p53
What does SV40 express during transformation?
Large T antigen
What does Tag do?
Binds to Rb and p53 and inhibits both
RNA viruses bring in oncogenes and integrate them randomly into the genome
True
Retroviruses can carry oncogenes (_____) that were growth regulatory genes picked up from the host cell (____)
v-onc
c-onc
What is the functional difference between a v-onc and a c-onc?
none??
When a retrovirus containing an oncogene infects a cell, it can induce what?
Transformation
How do retroviruses have their genome replicated? What is the implication of this?
By inserting into the host genome
Insertion occurs randomly and may disrupt host genes
The site of insertion can determine the fate of the cell. What are the 3 ways a v-onc can insert itself?
- In the middle of a tumor suppressor gene (Rb) it will inactivate it = insertional inactivation
- If it inserts upstream of an oncogene, it can result in the overexpression of the oncogene and subsequent transformation
- In a way that is not harmful to the cell
Retrovirus insertion is especially bad because it includes what?
Enhancers, promoters, polyadenylation signals, exon signals, etc
What increases the odds that a retrovirus will insert into the genome at a oncogene/tumor suppressor gene?
These genes are being transcribed by the cell > the chromosome is in euchromatin state = more lose so it is easier for virus to insert its DNA
Rb, P21, P53 are common what?
Tumor Supressor
E2F, Cdk are common what?
Oncogenes
What may lead to the formation of tumors in immune-suppressed individuals?
Persistent viruses that are normally controlled by the immune system may be activated when the immune system is failing. The viruses which are normally not dangerous, go on to transform cells.
