9-17 Cancer Flashcards Preview

MCBG EXAM 3 FINAL > 9-17 Cancer > Flashcards

Flashcards in 9-17 Cancer Deck (42):
1

What are the 4 cellular Pathways NOT confined to 1 cell and also potentially affected by neighboring non-transformed cells

A: Promotion OR INhibition of Angiogenesis

B: Promotion OR INhibition of Metastasis

2

_____ cells often obtain an "immortality" ability.
2)What is "Immortality" ?
3) How do you measure Immortality of cells?

CANCER cells obtain "immortality" because they BLOCK APOPTOSIS.

2) Immortality= CA overproduction of telomerase allows CA cells to bypass telemere shortening
-->bypass p53 activation--->bypasses cell death smh

3) measure immortality by placing cells in nutrient
cell-culture and observing which cells last forever = cancer cells

3

What are the common resulting processes that occur from an Oncogene Pathway [5]

B) What do these processes similarly ALL end up leading to??

Oncogenes:
1. Promote Cell Division
2. BLOCK Apoptosis-->promotes Genetic Instability
3. Promote Immortality-->promotes Genetic Instability
4. Promote Angiogenesis
5. Promote Metastasis using EMT

B) All of these PROMOTE GROWTH AND MALIGNANCY OF TUMORS

4

1) What is EMT (____ ___ _____)?
2)What do EMT usually result in?
3) When is the process reversed into a MET

1) EMT(epithelial-->mesenchymal transition) = allows CA cell to metastasize from tumor mass and travel to target organ by degrading basal lamina/basement membrane

2) EMT usually result in a secondary tumor within a diff location! --->WHAT USUALLY KILLS THE PT

3) MET[reverse of EMT]= occurs when the CA cell has finally gotten to its target

5

A: What are 5 common processes that result from Tumor Suppressor Gene Pathways?
B: Which of these processes are affected by neighboring non-transformed cells unrelated to actual tumor?

A:
1. Stops Cell division
2. Encourages Apoptosis/cell death
3. Blocks Immortaility
4. Inhibit Angiogenesis
5. INhibits Metastasis

B: Inhibition of Angiogenesis&Inhibition of Metastasis

6

The Death Receptor pathway is an _____[intrinsic/EXtrinsic] pathway and is 1 of the 2 pathways involved in the _______
2) This pathway has potential to ____-____ with its sister pathway _____

Death Receptor Pathway is Extrinsic pathway and is 1 of the 2 involved in the DEATH CENTRAL DECISION BOX

2) Death Receptor Pathway "may" CROSS-TALK with its sister Death decision box pathway: [Mitochondrial Signal transduction pathway]

7

The mitochondrial signal transduction pathway is an _____[intrinsic/EXtrinsic] pathway and is 1 of the 2 pathways involved in the _______

2) This pathway has potential to ____-____ with its sister pathway _____. Both pathways lead to what?

mitochondrial signal transduction pathway is an intrinsic pathway and is 1 of the 2 involved in DEATH CENTRAL DECISION BOX

2) mitochondrial signal transduction "may" CROSS-TALK with its sister Death decision box pathway: [Death Receptor Pathway]----(both lead to)----> Caspase protease apoptosis and ultimate phagocytosis

8

Describe the mechanism behind the
____ Death Receptor pathway [3]

2) This pathway is effectively known as the ____ Rxn

EXTrinsic Death Receptor Pathway = DISC Rxn:

1st: free Adaptor proteins/FADD bind to cytoplasmic side of a Death Receptor/FAS and activates receptor

2nd: activated Death Receptor/FAS turns around to activate procaspase 8 or 10---->caspase 8 or 10

3rd: caspase 8 or 10 activates [Caspase Protease Cascade]!----> Apoptosis

9

A: What do activated BH Bak/Bax proteins do and where are they located?

B: [BH BcL2] ___[promotoes/BLOCKS] Apoptosis. How does it do this ?

C: When Cytochrome C is released from mitochondria what does it do?

A: Activated [BH BAKorBAX] of the mitochondrial membrane "punch holes" into tht membrane allowing cytochrome C to diffuse out -->creates Apoptosomes

B: [BH BcL2] BLOCKS Apoptosis by stopping mitochondria membrane damage and thus preventing cytochrome C passage to cell cytoplasm

C: Released after BH Bak/Bax punch holes in mitochon membrane..Cytochrome C diffuses out to activate procaspase 9 into caspase 9 which will join with Apaf1 to form APOPTOSOME!--->activated caspase 9 of Apoptosome activates caspase 3--->Finally initiates Apoptotic Caspase protease Cascade

10

PROMOTES Apoptosis = ________ gene

PROMOTES/ ENCOURAGES Apoptosis =TUMOR SUpressor GeNE
"PROfessional TUmors" smh

11

Describe mechanism behind the ___[intrinsic/EXtrinsic] mitochondrial signal transduction pathway [2]

intrinsic mitochondrial signal transduction pathway:

1st: [BH BcL2] mostly binds/inhibits [BH BAKorBAX] . but in this pathway, [BIDorBAD] OUTCOMPETE
[BH BAKorBAX] and binds to [BH BcL2] better.

2nd: ---> allows [BH BAKorBAX] oligomers to be freee now & eventually punch holes in mitochon membrane allowing Cytochrome C passage

12

Name 6 homolog members of BID Accessory Protein Family

2)What do these do?
3) What stimulates their production?

4) Are these PRO- or AnTi- Apoptosis?

BID Family: Bid / Bad / Noxa / Puma / Bik / Bim

2) OUTCOMPETES [BH BAKorBAX] for
[BH BcL2 binding site]-->frees/releases [BH Bak/Bax] for apoptosis

3) These Accessory Proteins production is stimulated by p53!

4)BID family is Pro- /Encourages Apoptosis and Tumor suppressor genes

13

1) Name 4 homolog members of the BcL2 family

2) BcL2 has a __pocket allowing it to bind to other ____ proteins. Ex: What does BcL2BAK and Bcl2BAX do?

3) Is this family PRO- or AnTi- Apoptosis?

BcL2 Family: for diff. cell types

2) BcL2 has binding pocket tht allows other BcL2-like proteins to join. Ex: BcL2BAK and BcL2BAX dimers BLOCK Apoptosis

3) BcL2 Family is always AnTi- / BLOCKS Apoptosis

14

1) When Caspase 9 is activated by _____, it combines with ____ and ____ to form an _______! What does Activated Caspase 9 activate to start the Apoptotic Caspase protease cascade??

2) What is XIAP?
3) What happens to XIAP when mitochondria is damaged?

When Caspase 9 is activated by diffused outward Cytochrome C, it combines with Cytochrom C and Apaf1 to form AN APOPTOSOME! **Activated Caspase 9 then activates CASPASE 3-->Caspase protease cascade

2) XIAP (X-linked INHIBITOR of Apoptosis)= found in cytoplasm this normally BLOCKS Apoptosis by stopping the activated Caspase 3
3) On mitochon damage, [Smac/DIABLO] blocks XIAP
----->ReActivates Caspase 3--->activates Apoptosis

15

[Smac/DIABLO] is an ____ of an ____ because it BLOCKS ______ (which would normally ........ )

2) Is [Smac/DIABLO] an oncogene or Tumor Supressor Gene{ProApoptosis]?

[Smac/DIABLO] is an inhibitor of an inhibitor because it BLOCKS [XIAP--which normally blocks activated Caspase 3)

2)[Smac/DIABLO] is ProApoptosis and thus a Tumor Suppresor Gene

16

AIF (___ ___ ___) and Endonuclease G ?
2) What stimulates the release of this crazy duo?
3) What other major cell event occurs during this release?

4)Is this duo PRO- or AnTi- Apoptosis?

BOTH TOGETHER enter nucleus and degrade DNA WITHOUT Caspase Protease help!

2)> are released when mitochondria membrane damage occurs from newly freed [BH BAKorBAX].

3) Also during this time...mitochon holes from
[BH BAKorBAX] allow Cytochrome C to diffuse out and create Apoptosome with activated caspase 9 and Apaf1

4)this crazi duo is ProApoptosis = Tumor Suppressor Genes

17

Apoptosomes consist of what componenets?

Apoptosome = Procaspase 9 + Apaf1

18

What are key events (5) that cause cellular "Stress" and thus activate ____ or ____ --->which lead to activating the [intrinsic Apoptotic mitochondrial signal transduction]

2)What event does NOT cause stress but can still cause [intrinsic Apoptotic mitochondrial transduction] ?

oxidants / High Ca+ / short telomeres / mitotic catastrophe / DNA damage--->"Cellular Stress"
.....and thus activate p53 or Ras pathway which lead to [intrinsic Apoptotic mitochondrial signal transduction pathway]

2)Growth Factor Withdrawal can cause the
[intrinsic Apoptotic mitochondrial transduction]

19

_____ has the interesting ability to activate Cell Division and Cell Apoptosis/Death (along with___ & _____). The decision of which will happen depends on what 2 factors?

2)Which component of the this pathway PROmotes Cell survival [2]

Ras-GTP activates Cell Division AND Cell Apoptosis/Death (along with Cell differentiation and Survival) [P] ---> BAD, mdm2 AND [IkB binding inhibitor of NFKB]= PROmotes cell survival and CA

20

How is abnormally HIGH levels of mitogenic Myc and E2F related to Cell-cycle arrest or Apoptosis

2)Would you consider Myc and E2F at HIGH levels to be oncogenes or Tumor Suppressor genes?

HIGH levels of -->activate Arf
---->Arf binds and pulls off Mdm2(which is the father binding/inhibitor of p53)) -->p53 is now released and free to either cause cell-cycle arrest OR Apoptosis depending on cell type & extracell conditions

2)HIGH levels of are Tumor Suppressor Genes when p53 is present ..but despite that are STILL TECHNICALLY ONCOGENES :-(

(opposite from function at normal levels)

21

1) Mdm2 ?

2) Why would Mdm2 DeTach from its main product (__)? [2]

Mdm2 =father ubiquitin ligase that binds p53 and encourages its degradation/destruction by proteosomes

2)*Mdm2 DeTaches from main product p53 when DNA damage stimulates kinases to phosphorylate p53. This separates p53 from Mdm2
OR
**Arf (activated by HIGH levels of Myc and E2F) binds and pulls Mdm2 off of p53

22

Properties of metastatic/malignant cell [6]

1. epithelial Metastatic CA cells undergo phenotypic EMT initially to travel "acquire stem-like look"
2. Mesenchymal metastatic cells invade the Type 4 collagen basal lamina and ECM
3. INC protease enzyme secretion (especially type 4 collagenases)
4. high conc. membrane laminin receptors and ECM integrin receptors enable motion
5. can survive at distant sites due to lack of need for growth survival or ECM factors
6. At target site metastatic cells REVERSE EMT (MET) for new propagation and growth

23

adenoma

benign glandular tumor tht remains inside Type 4 collagen basal lamina with NO INVASION

24

adenocarcinoma

MALIGNANT tumor in which invading cells have undergone EMT (epithelial-->mesenchymal transition) and have destroyed integrity of Type 4 collagen basal lamina/basement membrane

25

What are the 2 ways Mesenchymal transitioned tumor cells enter the bloodstream

2) [T or F] Most Tumor Cells that enter the bloodstream can survive the trip and eventually produce new tumors

A: Crossing the wall of a LYMPHATIC vessel which will eventually dumps its contents (including the tumor cells) into blood stream smh [more common]

B: crossing wall of a blood vessel and extravasate into tissue when @ new target

2) FALSE! less than 1/1000 tumor cells entering bloodstream survive

26

What causes lymph node metastases?

Tumor cells that have entered lymphatic vessels become trapped in the lymph nodes along the way-->lymph node metastases

27

A: What are the 3 Steps invasive tumor cells must do to cross the ___ _____ basal lamina

B: Why are invasive tumor cells such a threat to neighboring normal cells?

C: What also has a similar invasion process?

A: 1. tumor cells high conc. of laminin receptors bind to the laminin located inside the Type 4 collagen Basal lamina

2nd: Tumor cell secretes Both
[*Type 4 MMP ProCollagenase] which when activated digest Basal Lamina
AND
**Urokinase Plasminogen activator (uPA)=does same but

3rd: MOTILITY / TRAVERSE THRU!

B: invasive tumor cells can encourage normal neighboring cells to start doing the same invasive stuff!

C: Non-transformed endothelial cells in angiogenesis

28

1) uPA(___ _____ _____) is known for its ability to ......

2) How exactly does it do this? [3]

3) What does MMP stand for?

1) uPA(Urokinase Plasminogen Activator) enables invasive tumor cells to degrade [Type 4 Collagen basal lamina bsment membrane]
----------------------------------------------------------------------------
uPA activates ECM parent plasminogen by hydrolyzing its central peptide bond ---> creates active daughter [plasmin] protease

---> As a daughter [plasmin protease] the ORIGINAL
C-terminal end of parent plasminogen degrades/proteolysis [type 4 Collagen ECM] directly

AND activates some [type 4 MMP procollagenases]to help it!
-------------------------------------------------------------------------------
^MMP=matrix metallo-proteinase^

29

Where is plasminogen made and where is it mostly located?

Plasminogen is MADE in the liver but ubiquitously LOCATED all throughout the Extracellular Matrix

30

1) Angiostatin

2) Why would removing an old tumor possibly cause a new tumor to grow?

original N-TERMINAL END of plasminogen cleaved into smaller piece--> that actually does the opposite of C-terminal End [plasmin protease]

**oRIGINAL N-TERMINAL END STOPS ANGIOGENESIS! = NO TUMOR NUTRITION/BLOOD SUPPLY

2) N-Terminal End of old tumor is SUPPRESSING newer tumors from growing. When old is removed newer/SECONDARY tumor is able to grow

31

How are new blood vessels formed for Tumor Cell nutrition (AKA ___)? [3]

*Angiogenesis!
1st: tumor cells express pro-angiogenic factors (VEGF & FGF) that induce vascular endothelial cells to INC proteinases expression and inhibit proteinase inhibitor expression

2nd: These proteinases allow endothelial cells to invade vascular basement membrane & proliferate

3rd: After proliferation new blood vessels are formed and they supply tumor cells nutrients/oxygen as result

32

VEGF

Vascular Endothelial Growth Factor= secreted by Tumor Cells to create new blood vessel formation/angiogenesis

33

FGF

Fibroblast Growth Factor=secreted by Tumor Cells to create new blood vessel formation/angiogenesis

34

EnDOStatin

2)What enzyme cleaves the parent molecule of EnDOStatin to make the smaller piece?

original C-TERMINAL END of a [parent Collagen 18] fiber cleaved into smaller piece (endostatin)--(BLOCKS)----> ANgiogeneis! = does the opposite of C-terminal End from plasminogen parent

2) [parent Collagen 18] fiber is cleaved by an extracellular tumor protease----> endostatin

35

Avastin

2) What were the negative effects of this drug?

New therapy ANTIBODY that binds and inhibits VEGF(secreted from tumor cells for angiogenesis)

-Made tumors MORE aggressive due to overcompensation of tumor to replace VEGF

36

BRCA1

2)What thing has ability to turn UP BRCA1 activation and why would it do this?

tumor suppressor chromatin remodeling complex that decondenses DNA repair genes & p53 genes -->upregulates p53 ( therefore also upregulates [p21/waf1/CKI]

2) E2F UPREGULATE BRCA1 in (G1) to act as NEGATIVE FEEDBACK LOOP for when it's time to stop going into S-phase

37

In Grand Scheme: Why is CA associated with INHIBITION of Apoptosis? [2]

*CA cells are resistant to apoptosis and even with DNA damage apoptoic resistant CA cells survive.
*Many CA have elevated [BcL2] and mutatedORabsent p53

38

In Grand Scheme: Why is Autoimmune Disorders associated with INHIBITION of Apoptosis?

2) What is this usually caused by?

*Apoptosis-resistent B and T cells allow survival even after they've already done their job or reached certain stage
-->damage

2) caused by inactivating mutation in a Fas receptor gene or elevated [BcL2]

39

In Grand Scheme: Why are Viral Infections associated with INHIBITION of Apoptosis?

2) What's an example of this?

vitals give apoptosis-resistance to normal cells so that they can use those cells to reproduce itself b4 cell is killed.

2) Ex: [vBcL2 HOMOLOGS] and cRMA protease inhibitors prevent apoptosis

40

Why is AIDS associated with PROMOTION of Apoptosis?

HIV protein Nef down regulates gp120-CD4 receptors in infected cells but then secretes [gp120 FAS ligand] so it can bind to NON-infected cells and INC their apoptosis

41

Why is Neuodegenerative disorders (like _______) associated with Apoptosis PROMOTION?

Neurodegenerative dz (like Alzheimers) secrete abnormal proteins like beta-amyloid that induce apoptosis

42

Why does Ischemic injury PROMOTE Apoptosis?

injury to area requires reperfusion/release of blood blockage which brings along with it HIGH levels of Ca+, free radicals & oxidants--->all induce apoptosis of heart & brain cells