Cancer Genetics I (Sept. 17 - Schultz) Flashcards Preview

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Flashcards in Cancer Genetics I (Sept. 17 - Schultz) Deck (27):
1

List the 6 oncogenic pathways that lead to tumor growth and malignancy of tumors

1. Promote cell division
2. inhibit apoptosis
3. promote genetic instability
4. promote immortality
5. promote angiogenesis
6. promote metastasis

2

Describe the concept of cellular immortality

Normal cells have a finite # of cell divisions (30-35 generations) -> then cells go into senescence

Cancer cells will never go into senescence -> gives rise to the term immortality ->overexpression of telomerase (telomers never become short as they produce successive generations) -> immortal cell lines

3

What are the developmental pathway abnormalities that can lead to cancer?

Mutations in signaling pathways:
-Notch
-Wnt
-Hedgehog

4

List the 5 tumor suppressor gene pathways:

1. Inhibit cell division
2. Promote Apoptosis
3. Inhibit immortality
4. inhibit angiogenesis
5. inhibit metastasis

5

Describe the effects of protease activation (caspases) in the the apoptotic pathway of a cell that leads its phagocytosis

Protease activation through death receptor pathway causes:
1. Endonuclease activation
2. cell surface alteration
3. cytoskeletal reorganization

6

What are the 2 pathways that lead to the caspase cascade

Death Receptor pathway
&
Mitochondrial/ Signal Transduction Pathway

7

What does complex in the death receptor pathway which promotes caspase cascade?

DISC - Death inducing signaling complex

8

What causes the DISC composed of?

cytoplasmic adaptor proteins (i.e. FADD)

9

What procaspase is responsible for causing caspase cascade. (hint: this is activated by the DISC)

Caspase 8

10

What is the Death receptor pathway activated by?

TNF alphas -> FAS ligands

11

What is the difference between the extrinsic and intrinsic death pathway?

Extrinsic pathway is induced through death receptor pathway (neighboring cells secreting TNFs or GF withdrawal) -> extracellular ligands

Intrinsic pathway is induced through mitochondrial signal transduction pathway -> internal regulation/stress

12

What are the some of the factors that stress a cell and can induce intrinsic apoptotic pathway. (List of 5)

-DNA damage
-mitotic catastrophe
-short telomeres
-high Ca2+
-oxidants

13

How is mitochondria death pathway induced?

Bak/Bax proteins activate

14

What occurs once the Bak/Bax proteins are activated and how does the mitochondria pathway cause apoptosis?

Activation of Bak/Bax damage mitochondrial membrane and release cytochrome C -> activates caspase 9 -> induces caspase cascade

15

What is the function of Apaf1?

Apaf1 is an adaptor protein which works with cytochrome C to cleave caspase 9 and activate it.

16

What is the complex of mitochondrial death pathway called?

Apoptosome

17

True or False: Bcl-2 inhibits membrane damage and cytochrome C secretion from mitochondria.

True.
Bcl-2 inhibits membrane damage and cytochrome C passage into cytoplasm

18

What are the anti-apoptotic dimers?

Bcl-2; BCl-X-like + Bak; Bax

19

What are the pro-apoptotic dimers?

Bax/Bak oligomers

20

How does the mitochondria switch to induce pro-apoptotic factors?

Bid; Bad
Compete for Bcl-2 causing dossication of Bak and Bax from Bcl-2.

21

What is the inhibitor of inhibitor pathway? (Hint: Think about this devil of a protein)

Smac/Diablo

22

What is XIAP?

X-linked Inhibitor of apoptosis (inhibit caspase 3)

23

True/False: XIAP is not normally found present in the cytoplasm

False; normal levels of XIAP are found in cytoplasm. They work to inactivate caspase 3

24

How are Smac/Diablo and XIAP related?

Smac/Diablo production inhibits XIAP which allows activation of caspase 3 and create apototic causing substrates

25

Out of these factor proteins, which promote apoptosis? Which inhibit apoptosis?
-Bax;Bak
-Bcl-2;Bcl-Xl
-Bid;Bad
-Smac/Diablo
-XIAP
-AIF;Endo G
-p53

Pro-Apoptotic:
-Bax;Bak
-Bid;Bad
-Smac/Diablo

Anti-Apoptotic:
-Bcl-2;Bcl-Xl
-XIAP

26

Describe invasion of timor cells

-Tumor cells secrete Urokinase Plasminogten activator
-Allows Plasminogen to turn into plasmin
-Plasmin activates procollagenases into collageneses
-Allows proteolysis of collagen and invasion of tumor cells through blood vessels

27

What are some pro-angiogenic growth factors?

VEGF and FGF
(vascular endothelial growth factor and fibroblast growth factor)