Biochemistry of Cancer Flashcards
1
Q
hallmark of common cancers
A
- disordered proliferation, growth, and differentiation
- is a genetic disease
2
Q
heredity of Rb
A
- having one mutated copy puts you at an increased risk for developing retinoblastoma
- loss of the other copy of the gene causes tumor formation
3
Q
description of retinoblastoma
- cell type and location
- mutations
- forms
- other types of cancer
A
- arise from neural precursors in the immature retina
- an unusually small number of mutations are necessary to develop the cancer
- two forms, one hereditary and the other not
- Rb is frequently missing in many types of cancer
4
Q
E2F
A
- a TF typically bound by the active form of Rb
- this TF is responsible for sending the cell into a proliferative state
- specifically sending the cell into S phase
5
Q
mechanism of pRb
A
- in a nondividing cell, pRB is bound to E2F in the nucleus, inhibiting it from initiating transcription of proteins that will send the cell into s phase
- in a dividing cell, Cyclin D and E and their designated CDK’s will Phosphorylate pRb, causing it to release E2F
- E2F then goes on to initiate transcription of pro-mitotic genes
- most antiproliferative signals are funneled through Rb
6
Q
p53 is stabilized and increased…
A
during times of stress
-this is done by phosphorylation of p53
7
Q
Response elements or enhancer elements
A
-genes regulated by p53 have these regions and respond to p53
8
Q
Role of p53 in halting the cell cycle and apoptosis
A
- DNA damage: p53 then activates p21 which then inhibits Cyclin/CDK complexes, halting mitosis
- Ocogene expression: p53 is activated and tells the cell to begin apoptosis via induction of genes which produce reactive oxygen species (ROS)
9
Q
p21
A
- is activated by p53 when it senses damaged DNA
- p21 binds cyclin/CDK complexes which halts the cell cycle
- also is able to bind PCNA to inhibit progression of the replication fork
10
Q
RB tumor
A
retinoblastoma
11
Q
p53 tumor
A
sarcomas, carcinoma, and more
12
Q
NF1 tumor
A
neuroblastoma
13
Q
APC tumor
A
colon, stomach
14
Q
BRAC1 tumor
A
breast cancer
15
Q
oncogenes
A
- due to altered components of pathways that activate cell division in response to growth factor stimulation
- this is typically a dominant effect (only one mutated copy needed)
16
Q
proto-oncogenes
A
-typically involved in signal transduction in some way
17
Q
tumor cells generate many of their own…
A
growth factors
18
Q
signal transduction
-tyrosine kinase
A
- certain receptors penetrate the plasma membrane (ie PDGF receptors = tyrosine kinase)
- phosphorylation of tyr residues allow interaction with other members of the cascade
- signals are meant to be transient
19
Q
alterations in signal transduction cascades associated with cancer
A
- excess growth factor
- defective growth factor
- defective signaling molecules
- altered regulation of transcription factors
20
Q
altered growth factors
-simian sarcoma virus
A
- the simian sarcoma oncogene was originally identified in a transformaing retrovirus
- the gene encodes part of the PDGF molecule and is able to induce signal transduction
21
Q
Altered growth factor receptors
-EGF
A
- mutant forms of the epidermal growth factor receptor are known that constantly stimulate growth even in the absence of EGF
- family members include ErbB/HER2
22
Q
activation of RAS signalling
A
- this is a very important signaling molecule
- when bound to GTP, it is active
- When bound to GDP, it is inactive
- GAPs (GTPase activity protein) help regulate its activity
- mutations in RAS reduce GTPase activity, leaving it consitutively on
23
Q
NF1 gene and neurofibromin
A
- NFI encoded neurofibromin
- neurofibromin contains a GAP domain
- neurofibromatosis is associated with cafe-au-lait spots and benign neurofibromas
- the disease is associated with defective transduction, possibly through RAS
24
Q
expression of c-fos and c-jun
A
- in normal cells there is typically just one copy of each of these TF’s and therefore you get transient growth
- in cancerous cells, there are many copies of both which leads to continuous growth
- these TF’s bind to the AP1 site
25
Myc
- E boxes
- HATs
- myc encodes a transcription factor that regulates the expression of about 15% of all genes
- it binds to enhancer sequences (E boxes) and recruits histone acetyltransferses (HATs)
- mutated forms of myc are found in cancer cells, this leads to the up-reg of many genes, some of which are involved in prolif
26
burkitt's lymphoma translocation
- between 8 and 14
- puts a much stronger promoter associated with myc
- myc is now associated with a IgH promoter
27
burkitts lymphoma
- chromosomal translocations are associated with leukemia and lymphoma
- in this translocation, myc is placed with IgH and myc is then constitutively expressed
28
cyclin dysregulation
-excessive or innapropriate expression of cyclins is associated with some malignancies
29
role of SV40 T-antigen in tumor formation
- viral protein binds both pRb and p53 causing the cell to have no control over the entry into S phase
- Rb is not permitted to bind up E2F and p53 can not act as a safety brake
30
HPV in forming tumors
- has two proteins involved, E6 and E7
- E6: protein product capable of binding p53 and inducing its proteolysis
- E7: protein product capable of binding pRb and preventing it from interacting with E2F
31
acquired capabilities of cancers and the examples of genes involved
- self sufficiency in growth signals: RAS
- insensitivity to anti-growth signals: pRb
- tissue invasion and metastasis: inactivated E-Cadherins
- limitless replication potential: overly active telomerase
- sustained angiogenesis
- evading apoptosis: p53
32
chromosome chaos and cancer
-rearrangement and changes in chromosomes as a whole is thought to play a key role in the development of cancer
