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2020 MHS Genetics Unit2 > cancer > Flashcards

Flashcards in cancer Deck (90)
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1

a tissue with abnormally high cell number (neoplasm)

tumor

2

a malignant tumor that invades other tissues (metastasizes)

cancer

3

describe the phases of cell cycle

1 -cell growth

s-DNA replication

2-rapid cell growth

m-separation of sister chromatids, cytokenesis

0-differentiated, senescent

4

describe the important sites of quality control in the cell cycle (excluding cyclin)

  1. restriction point
    1. G1
    2. arrests cyclce if no extracellular growth signal  is present
  2. DNA damage checkpoints
    1. G1,SG2
    2. arrests cyclce if DNA damage is detected, initates repair
  3. DNA replication checkpoint
    1. S
    2. Arrests cycle if the replication fork is stalled, initiates repair
  4. metaphase checkpoint
    1. arrests cycle until all chromosomes correctly attach to the mitotic spindle

5

what are the signals that keep the cells in G0?

  1. TGF-B
    1. induces differentiation of cells
  2. contact inhibition
    1. cell-cell interactions through cadherin receptors
  3. telomere shorteninig
    1. cell senescene to avoid loss of genetic material

6

a cell is unable to repair the stalled replication fork what can be assumed about this cell?

The cell is stuck or DNA break in the S phase

  • p53(TF) increases->
    • increases p21(CKI)->arrests cell cycle
    • GADD45(DNA repair enzyme)
  • not repaired?
    • apoptosis initiated
      • IGF-BP3
        • inhibits apoptotic signal
      • Bax
        • activates apoptosis

cyclin DEAB

  1. function
    1. proteins regulated by transcription and proteolytic degradation (ubuiquitin)
    2. activate specific cyclin dependent kinases 
      1. phosphorylate target proteins
      2. promote cell cycle progression
  2. regulation
    1. inducible
      1. cyclin
      2. Cycin dependent kinase inhibitor (CDKI)- binds to the cyclin-CDK complex
        1. additional other kinases and proteasomal degradative regulators are availabe
    2. constitutive
      1. cyclin dependent kinases (CDK)

 

7

phosphorylate target proteins and promote cell cycle progression

cyclin DEAB

  1. function
    1. proteins regulated by transcription and proteolytic degradation (ubuiquitin)
    2. activate specific cyclin dependent kinases 
      1. phosphorylate target proteins
      2. promote cell cycle progression
  2. regulation
    1. inducible
      1. cyclin
      2. Cycin dependent kinase inhibitor (CDKI)- binds to the cyclin-CDK complex
        1. D-CKI binds to D-CDK, inhibiting the phosphorylation of Rb. Rb can dephosphorylate or be destroyed and replaced->reassociating with E2F ->E2F-Rb, stops the progress from G1->S
        2. additional other kinases and proteasomal degradative regulators are availabe
    2. constitutive
      1. cyclin dependent kinases (CDK)
        1. growth factor stimulates Ras-Mek pathway activating D-CDK phosphorylates Rb, on the E2F-Rb complex. Rb releases E2F is a transcription factor that leads to integral genes for cell cycle progression to continue.

 

8

describe the cyclins and their involvment in the cell cycle

  1. function
    1. proteins regulated by transcription and proteolytic degradation (ubuiquitin)
    2. activate specific cyclin dependent kinases 
      1. phosphorylate target proteins
      2. promote cell cycle progression

 

9

Describe how the extracellular signals lead to the generation of cyclin proteins

growth factors are critical to cell growth and diversity

  1. mitogens
    1. growth factors->receptor Y-kinase-> Ras->
  2. mitogen acivated kinase cascades (MAPkinase cascades)
    1. cRaf->MEK->Erk1/2
  3. other kinases and transcription factors
    1. p90rsk, cyclinD, etc
    2. growth

10

Ras has decreased in stimulation, what is required to activate this pathway? What important MAPkinase cascade does Ras acivate?

growth factors are critical to cell growth and diversity

  1. mitogens
    1. growth factors->receptor Y-kinase-> Ras->
  2. mitogen acivated kinase cascades (MAPkinase cascades)
    1. cRaf->MEK->Erk1/2
  3. other kinases and transcription factors
    1. p90rsk, cyclinD, etc
    2. growth

11

Cells require cyclin to move through the restriction points and to progress to the different cell cycles. What do extracellular signals promote during this process?

growth factors are critical to cell growth and diversity

  1. mitogens
    1. growth factors->receptor Y-kinase-> Ras->
  2. mitogen acivated kinase cascades (MAPkinase cascades)
    1. cRaf->MEK->Erk1/2
  3. other kinases and transcription factors
    1. p90rsk, cyclinD, etc
    2. growth

12

describe the parameters that must be met in to commit to moving from the G1 phase in cell cycle replication. Think of the items that occur in G1, a cellmoving out of scensence

  1. Adequate cell growth
    1. must preced DNA replication in S
  2. Restriction point
    1. G1/S transition is controlled by the restriction point
  3. sufficient cylcin D
    1. the transition point can only be passed if sufficient cyclin D is present
    2. cell growth will cause gradual increase in cycling D levels

debatable- decrease in the factors keepin the cell in G0=TGF-B

13

the gate keeper of the restriction point

Retinoblastoma protein (Rb) is the gatekeeper of the restriction point

  1. phosphorylation by D-CDK complexes inactivates Rb, and allows E2F trasncription factor to initiate cell cycle progression

14

E2F-Rb never dissociates. What did not happen in 

any of the following may have happend

  1. Growth factor did not stimulate the cell
    1. any where during this pathway may have been hindered
  2. Ras/Raf signal pathway did not induce synthesis of Cyclin D
  3. CyclinD was not transcribed with high enough concentrations
  4. CKI bound to E2F, may piggy back on #3

Retinoblastoma protein (Rb) is the gatekeeper of the restriction point

  1. phosphorylation by D-CDK complexes inactivates Rb, and allows E2F trasncription factor to initiate cell cycle progression

15

A DNA strand breaks or the suffers from a replication fork stall. What is the most likely of spots for this to happen and how is it handeled?

Ensure genomic integrity during interphase

  1. if DNA is damaged, cell cycle is halted and repair is initiated
  2. if repari is unsuccesful, apoptosis is initiated

certtain checkpoints are in place for detection of such events

  1. DNA damage checkpoints
    1. G1,S,G2
    2. arrests cycle if DNA damage is detected, initate repairs
  2. DNA replication checkpoint
    1. S
    2. arrests cycle if the replication fork is stalled, initiates repairs

16

what is the main transducer leading to cell cycle arrest. Explain 

Ensure genomic integrity during interphase

  1. if DNA is damaged, cell cycle is halted and repair is initiated
  2. if repari is unsuccesful, apoptosis is initiated

17

what is the purpose of DNA damage/checkpoints?

Ensure genomic integrity during interphase

  1. if DNA is damaged, cell cycle is halted and repair is initiated
    1. P53(TF)increases->
      1. p21
        1. is a CKI
      2. GADD45
        1. Repair DNA damage
  2. if repair is unsuccesful, apoptosis is initiated
    1. IGF-BP3
      1. inhibits anti-apoptotic signals
    2. Bax
      1. activates apoptosis

18

UV damage has caused DNA damage. when will the cell have a chance to become aware of this and how will it respond?

Ensure genomic integrity during interphase

  1. stages of potential cognizants
    1. G1,S,G2
  2. if DNA is damaged, cell cycle is halted and repair is initiated
    1. P53(TF)increases->
      1. p21
        1. is a CKI
      2. GADD45
        1. Repair DNA damage
  3. if repair is unsuccesful, apoptosis is initiated
    1. IGF-BP3
      1. inhibits anti-apoptotic signals
    2. Bax
      1. activates apoptosis

19

A cell undergoes replication fork stall. When will the cell have the oppotunity to gain aware of this?

20

A cell undergoes DNA damage. When will the cell have the oppotunity to gain aware of this?

21

describe the proteins that are activated and how leading to cell death?

caspases are cysteine proteases

  • proenzymes acivated by protelytic cleavage
    • initators (8,9,10)
      • activated directly by the death cell receptor and mitochondrial pathway
    • execution(3,6,7)
      • activated by initiator caspases
      • cleave many different proteins in the cell
        • actin
        • proteins of the nuclear envelope
        • DNA repair enzymes (GADD45)
        • inhibitors of caspase dependent endonucleases
  1. normal physiological process 
    1. embryogenesis
    2. maintenance of proper cell number
    3. removal of injured cells
  2. inition pahways
    1. Both pathways eventually will activate the caspase cascade (prenzymes activated by either method) intracellularly
      1. death receptor
      2. mitochondrial
  3. outcome
    1. caspase cascade leads to 
      1. chromatic condensation
      2. DNA fragmentation
      3. cell shrinkage
      4. cell fragmentation

22

GADD45 is unable to complete its job, what is the cell going to do next?

He is going to get chopped up by the execution caspases (3,6,7)

  1. normal physiological process 
    1. embryogenesis
    2. maintenance of proper cell number
    3. removal of injured cells
  2. inition pahways
    1. Both pathways eventually will activate the caspase cascade (prenzymes activated by either method) intracellularly
      1. death receptor
      2. mitochondrial
  3. outcome
    1. caspase cascade leads to 
      1. chromatic condensation
      2. DNA fragmentation
      3. cell shrinkage
      4. cell fragmentation

23

what is the purpose of apoptosis

  1. normal physiological process 
    1. embryogenesis
    2. maintenance of proper cell number
    3. removal of injured cells
  2. inition pahways
    1. Both pathways eventually will activate the caspase cascade (prenzymes activated by either method) intracellularly
      1. death receptor
      2. mitochondrial
  3. outcome
    1. caspase cascade leads to 
      1. chromatic condensation
      2. DNA fragmentation
      3. cell shrinkage
      4. cell fragmentation

24

A CT-cell tells a cancerous cell to die. What is the pathway?

death receptor of apoptosis

  1. initiator caspases are activated
    1. 8,9,10
  2. Execution caspase are activate
    1. 3,6,7
      1. activate Bid
        1. stimulates the mitochondrial pathway
      2. chromatin condensation
      3. DNA fragmentation
      4. cell shrinkage

25

Bax is generated but relies on what else to be operational?

  1. DNA damage repair was unsuccesful 
    1. IGF-BP3
      1. anti-apoptotic signal
    2. Bax
      1. CDKI
  2. Bax will supress the CDK and there will be a decline in cyclin. Stopping the cell growth
  3. death signal is sent to the mitochondria and the causes the release of cyt-c
  4. cyt-c binds to tapoptotic pretease activating factor-1 (Apaf-1)
  5. Apaf-1 -cyt-C complex activates the initiation caspase-9
  6. Caspase 9 activates exectution caspases - 3,6,7
    1. Bid activation
      1. Bid binds to Bax and BidBax complex generates a channel in the mitochondrial membrane
    2. chromatin condensation
    3. DNA fragmentation
    4. cell shrinkage

26

The constant expression of IGF-BP3 and Bax leads has what outcome?

  1. DNA damage repair was unsuccesful 
    1. IGF-BP3
      1. anti-apoptotic signal
    2. Bax
      1. CDKI
  2. Bax will supress the CDK and there will be a decline in cyclin. Stopping the cell growth
  3. death signal is sent to the mitochondria and the causes the release of cyt-c
  4. cyt-c binds to tapoptotic pretease activating factor-1 (Apaf-1)
  5. Apaf-1 -cyt-C complex activates the initiation caspase-9
  6. Caspase 9 activates exectution caspases - 3,6,7
    1. Bid activation
      1. Bid binds to Bax and BidBax complex generates a channel in the mitochondrial membrane
    2. chromatin condensation
    3. DNA fragmentation
    4. cell shrinkage

27

The body begins to decrease the growth factor att certain ages, what happens to some cells as this decline is complete?

apoptosis depends on the ratio of pro- anti-apoptotic molecules. A decrease in the growth factors leads to and increase in Bid. Bid must compete with Bcl-2 to find Bax.

  1. pro-apoptotic
    1. Bax
      1. form channels in the outer mitochondrial membran to release Cyt-C, butt function depends on binding of Bh3-only members (Bid)
    2. Bid
      1. regulare tthe activity of the channel forming pro-apoptotic factors
  2. anti-apoptotic
    1. Bcl-2
      1. sequesters BH3-only members away from the channel forming pro-apoptotic factos
      2. can bind and inativate Apaf-1

28

list the important pro-/anti- apoptotic factors and their operation

  1. pro-apoptotic
    1. Bax
      1. form channels in the outer mitochondrial membran to release Cyt-C, butt function depends on binding of Bh3-only members (Bid)
    2. Bid
      1. regulare tthe activity of the channel forming pro-apoptotic factors
  2. anti-apoptotic
    1. Bcl-2
      1. sequesters BH3-only members away from the channel forming pro-apoptotic factos
      2. can bind and inativate Apaf-1

29

Smoking increases exposure of what chemicals? how does this affect the cell?

carcinogens and radiation cause DNA modification

  1. smoking increases polycyclic hydrocarbon exposure, which turns in to epoxides and alters DNA. An alteration in the DNA may lead to lung cancer

look at the sequential order benign->malignant

 

30

describe the formation of cancer

look at the sequential order benign->malignant