Tumor biology and metastasis (Withrow)

Question 1

List CDKs and their cyclins.

Answer 1

CDK 4, 6/cyclin D
CDK 2/cyclin A
CDK 2/cyclin E
CDK 1/ cyclin B

Question 2

Phosphorylation at _____ and ______ residues suppresses activity of CDK/cyclin complexes.

Answer 2

threonine and serine

Question 3

List the two families of CDK inhibitors, examples of each, and their targets.

Answer 3

• INK4A family (p15, p16, p18, p19): primarily act on CDK 4 and 6 complexes
• CIP/KIP family (p21, p27, p57): less specific; p21 has affinity for G1 complexes

Question 4

______ and ______ are two key protein kinases involved in DNA damage responses and are considered “sensors”.

Answer 4

ATM and ATR

Question 5

ATM targets _______.

Answer 5

p53

Question 6

ATM and ATR can target _____ , family of phosphatases, for phosphorylation which can block cyclin-CDK activity and thus inhibit cell cycle progression.

Answer 6

cdc25

Question 7

p21 has a high affinity for ______ complexes and acts as CDKI.

Answer 7

G1 CDK/cyclin

Question 8

The p53 response to stress is largely mediated through the _____ kinase and leads to the phosphorylation of _____ of p53.

Answer 8

ATM
N terminus

Question 9

_______ acts as a negative regulator of p53 and is also a transcriptional target of p53.

Answer 9

MDM2

Question 10

______ and _______ are members of the death receptor family.

Answer 10

TNF and Fas

Question 11

FADD binding leads to activation of __________ and downstream activation of _____ for apoptosis.

Answer 11

caspase 8
effector caspases

Question 12

If cells are damaged, p53 can upregulate ______ and cause cell cycle arrest or can aid in directing the cell into apoptosis through upregulation of ______ or downregulation of ______.

Answer 12

• p21
• Bax
• Bcl2

Question 13

Oncogene mutations occur in ____ cells.

Answer 13

somatic

Question 14

What type of mutation occurs in oncogenes?

Answer 14

dominant gain of function

Question 15

What type of mutation occurs in tumor suppressor genes?

Answer 15

recessive loss of function

Question 16

Tumor suppressor gene mutations can occur in what type of cells?

Answer 16

both germline and/or somatic

Question 17

_______ proto-oncogenes encode proteins with GTP-ase and GTP-binding activity, and in normal cell, help modulate cellular proliferation.

Answer 17

Ras

Question 18

What oncogene is involved in childhood neuroblastoma and by what mechanism is it activated?

Answer 18

Myc
gene amplification

Question 19

In canine STS, 20% were found to have _____ mutation and 11.4% were found to have ______ amplification.

Answer 19

p53
MDM2

Question 20

______ is a classic example of a oncogene activation through point mutation.

Answer 20

Ras

Question 21

The inherited form of retinoblastoma occurs in ___% of cases. What is its mode of inheritance? What does this mean for children who have this inheritance?

Answer 21

• 40%
• dominant with incomplete penetrance
• about 50% of children are affected by the condition

Question 22

Most anti-proliferative signals are funneled through ______.

Answer 22

Rb protein

Question 23

_____ and _____ are TSGs involved in contact inhibition.

Answer 23

NF2 and LKB1

Question 24

What soluble factor activates epithelial to mesenchymal transition (EMT)>

Answer 24

TGF-B

Question 25

______ is a tumor suppressor protein that counteracts PI3K signaling.

Answer 25

PTEN

Question 26

The telomerase complex consists of an RNA subunit that contains a domain complementary to the telomeric repeat sequence ________ and a catalytic protein component.

Answer 26

TTAGGG

Question 27

______ and ______ are 2 prominent signaling molecules involved in formation of tumor-associated vasculature.

Answer 27

VEGF and basic fibroblast GF

Question 28

What is anoikis?

Answer 28

Programmed cell death associated with loss of cellular contact

Question 29

In addition to cancer cells, _____ and _____ cells have ability to invade tissue planes and cross vascular barriers.

Answer 29

leukocytes and neuronal cells

Question 30

______ is a metastasis promoting gene that codes for a protein that connects actin skeleton to cell membrane.

Answer 30

ezrin

Question 31

The degree of _______ expression in primary tumor of dogs with OSA was shown to predict a more aggressive clinical course of disease, defined by metastasis to the lung.

Answer 31

ezrin

Question 32

Activity of MMPs in ____ and ____ have been correlated with grade and metastatic propensity.

Answer 32

OSA and MCTs

Question 33

_____, ____, and ____ are a family of transcription factors that are thought to contribute to epithelial to mesenchymal transition (EMT).

Answer 33

Twist, snail, slug

Question 34

Cell-matrix anchorage is mediated primarily by transmembrane receptors referred to as ______.

Answer 34

integrins

Question 35

Cell to cell interactions are mediated by a family of calcium-binding glycoproteins referred to as ____.

Answer 35

cadherins

Question 36

Anoikis is prevented by what two systems in normal tissues?

Answer 36

cell-matrix anchorage and cell to cell interactions

Question 37

The overexpression of integrin pair _____ subverts the need for ligand binding and results in generation of survival signals in malignancy.

Answer 37

AvB3

Question 38

List 4 proteins that are reported to be involved in resistance to anoikis by tumor cells?

Answer 38

- tropomyosin receptor B kinase (TrkB) - Focal adhesion kinase (FAK) - Galectin-3 - TGF-B

Question 39

____ is a specific adhesion molecule initially identified as the receptor for the matrix component hyaluronic acid on hematopoietic cells.

Answer 39

CD44

Question 40

______ and _____ are often amplified in canine low-grade OSA and their dedifferentiated counterparts.

Answer 40

MDM2 and CDK4

Question 41

MDM2 gene is altered in ___% of canine OSA compared to ____% of tumors that have inactivating mutations in TP53.

Answer 41

3% 95%

Question 42

Well-differentiated and dedifferentiated liposarcomas are distinct neoplastic entities characterized by _____ expression, which may represent a useful diagnostic and potentially prognostic marker for canine liposarcoma.

Answer 42

MDM2