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Flashcards in Biochemistry of Cancer Deck (32)
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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
Q

Myc

  • E boxes
  • HATs
A
  • 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
Q

burkitt’s lymphoma translocation

A
  • between 8 and 14
  • puts a much stronger promoter associated with myc
  • myc is now associated with a IgH promoter
27
Q

burkitts lymphoma

A
  • chromosomal translocations are associated with leukemia and lymphoma
  • in this translocation, myc is placed with IgH and myc is then constitutively expressed
28
Q

cyclin dysregulation

A

-excessive or innapropriate expression of cyclins is associated with some malignancies

29
Q

role of SV40 T-antigen in tumor formation

A
  • 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
Q

HPV in forming tumors

A
  • 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
Q

acquired capabilities of cancers and the examples of genes involved

A
  • 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
Q

chromosome chaos and cancer

A

-rearrangement and changes in chromosomes as a whole is thought to play a key role in the development of cancer