Biochemistry of Cancer

Question 1

hallmark of common cancers

Answer 1

• disordered proliferation, growth, and differentiation

- is a genetic disease

Question 2

heredity of Rb

Answer 2

• having one mutated copy puts you at an increased risk for developing retinoblastoma
• loss of the other copy of the gene causes tumor formation

Question 3

description of retinoblastoma

• cell type and location
• mutations
• forms
• other types of cancer

Answer 3

• 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

Question 4

E2F

Answer 4

• 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

Question 5

mechanism of pRb

Answer 5

• 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

Question 6

p53 is stabilized and increased…

Answer 6

during times of stress

-this is done by phosphorylation of p53

Question 7

Response elements or enhancer elements

Answer 7

-genes regulated by p53 have these regions and respond to p53

Question 8

Role of p53 in halting the cell cycle and apoptosis

Answer 8

• 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)

Question 9

p21

Answer 9

• 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

Question 10

RB tumor

Answer 10

retinoblastoma

Question 11

p53 tumor

Answer 11

sarcomas, carcinoma, and more

Question 12

NF1 tumor

Answer 12

neuroblastoma

Question 13

APC tumor

Answer 13

colon, stomach

Question 14

BRAC1 tumor

Answer 14

breast cancer

Question 15

oncogenes

Answer 15

• 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)

Question 16

proto-oncogenes

Answer 16

-typically involved in signal transduction in some way

Question 17

tumor cells generate many of their own…

Answer 17

growth factors

Question 18

signal transduction

-tyrosine kinase

Answer 18

• 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

Question 19

alterations in signal transduction cascades associated with cancer

Answer 19

• excess growth factor
• defective growth factor
• defective signaling molecules
• altered regulation of transcription factors

Question 20

altered growth factors

-simian sarcoma virus

Answer 20

• 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

Question 21

Altered growth factor receptors

-EGF

Answer 21

• 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

Question 22

activation of RAS signalling

Answer 22

• 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

Question 23

NF1 gene and neurofibromin

Answer 23

• 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

Question 24

expression of c-fos and c-jun

Answer 24

• 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

Question 25

Myc

• E boxes
• HATs

Answer 25

• 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

Question 26

burkitt’s lymphoma translocation

Answer 26

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

Question 27

burkitts lymphoma

Answer 27

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

Question 28

cyclin dysregulation

Answer 28

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

Question 29

role of SV40 T-antigen in tumor formation

Answer 29

• 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

Question 30

HPV in forming tumors

Answer 30

• 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

Question 31

acquired capabilities of cancers and the examples of genes involved

Answer 31

• 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

Question 32

chromosome chaos and cancer

Answer 32

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