W3- Lecture 16.3- Neoplasm 3

Question 1

What is pathogenesis ?

Answer 1

mechanism that causes the disease

Question 2

Name the 10 hallmarks of cancer

Found by Weinberg and hanahan

Answer 2

Sustaining proliferating signalling 
Evading growth suppressors 
Enabling relicative immortality 
Activating invasion & metastasis 
Inducing angiogenesis 
Resisting cell death 

Avoiding immune destruction
Tumour-promoting inflammation
Genome instability & mutation
Disregulating cellular energetics

Question 3

Name the 6 hallmarks of cancer

Answer 3

Self sufficient growth signals 
Insensitive to anti-growth signals 
Tissue invasion and metastasis 
Limitless replication potential 
Sustained angiogenesis 
Evading apoptosis

Question 4

What is a proto-oncogene

Answer 4

normal gene that can become an oncogene (cancer-producing gene) due to mutations or increased expression

Question 5

Which two major classes of regulatory molecules determines a cells progression through the cell cycle

Answer 5

Cyclins

Cyclin-dependant kinases

Question 6

How are cyclin dependant kinases activated by cyclins

Answer 6

Via phosphorylation

Question 7

Describe growth factor signalling

Answer 7

Growth factor in extracelliular fluid
Binds to receptor on cell membrane
Induces activation of protein
Signal transduction cascade - ends in nucleus
Activates growth promoting genes
Activates cyclins and CDKs+ drives cell cycle progression

Question 8

Name 4 ways that during tumorigenesis a cell can acquire a growth advantage by self sufficiency in growth signals

Answer 8

secrete a growth factor for which the cell already expresses the receptor

Components of the signal transduction pathway are mutated and become constitutively activated.

Transcription factors controlling Cyclin expression are mutated and become constitutively activated.

The cyclin and CDK protein complexes that drive cell cycle become over-expressed

Question 9

What is an autocrine loop

Answer 9

Atypeofinteractionbetweengrowth factors,cytokinesandtargetcells,in which acellproducesthesamegrowth factorsandcytokinesforwhichithas receptors

Question 10

Describe Platelet-derived growth factor(PDGF)

Answer 10

one of the numerousgrowth factors, orproteinsthat regulatecellgrowth anddivision. In particular, it plays a significant role inblood vessel formation(angiogenesis),

Question 11

what are Glioblastomas?

Answer 11

Form of aggressive brain cancer

Question 12

What is a Transforming growth factor/tumour growth factor/TGF

Answer 12

Used to describe two classes ofpolypeptidegrowth factors,TGFαandTGFβ.

produced inmacrophages,braincells, andkeratinocytes, and inducesepithelialdevelopment

Question 13

What are sarcomas ?

Answer 13

are malignant tumorsmade ofcancellous bone,cartilage,fat,muscle,vascular, orhematopoietictissues

Question 14

What are Fibroblast growth factors, orFGFs ?

Answer 14

family ofgrowth factors, with members involved inangiogenesis,wound healing.

Question 15

What are Hepatocyte growth factor/scatter factor(HGF/SF)

Answer 15

aparacrine(cell-cell communication) cellular growth,motilityandmorphogenic factor.

Question 16

In what cancers would we find

Platelet Derived GF
Tumour GFa
Fibroblast GF
Hepatocyte GF

Answer 16

glioblastomas (brain cancer).

sarcomas (cancers of bone/fat/cartilage origin).

melanomas

thyroid tumours

Question 17

Describe the Ras oncogene

Answer 17

Ras is a member of a family of G proteins.
Inactive Ras is bound to GDP and active Ras is bound to GTP.
Active Ras then activates signal transduction cascade (eg MAP kinase pathway).
Certain point mutations of Ras keep it in its active state, and drive signal transduction.

Question 18

How is an active Ras activated

Answer 18

Inactive Ras is bound to GDP and active Ras is bound to GTP.

Question 19

Why does a mutation of Ras drive signal transduction

Answer 19

The mutation stops the inactivation of Ras so it stays active and constantly signals the dive of cell cycle

Question 20

What is myc ?

+ over expression causes ?

Answer 20

transcription factor expressed in most cells.

Myc activates transcription of several growth promoting genes (eg cyclins and cyclin dependent kinases)

Myc represses transcription of several growth inhibiting genes (eg CDK inhibitors).
Over-expression of Myc increases its activity and drives expression of growth promoting genes.

Over-expression = hyperplasia

Question 21

Name a Transcription factor that controls cyclin expression

Answer 21

Myc

Question 22

Where is myc oncogene over-expressed ?

Answer 22

breast, colon and lung carcinomas, and in Burkitt’s lymphoma.

Question 23

Name one cyclin and one CDK that are often over-expressed in cancer
+ type of cancer

Answer 23

Cyclin d
-breast, oesophagus and liver carcinomas

CDK4
-melanomas, sarcomas and glioblastomas.

Question 24

Name three cell cycle inhibitor

that when distrusted over-proliferation cell may take place

Answer 24

retinoblastoma protein (Rb).
 p53.
 Cdk inhibitors (eg p16, p21)

Question 25

Describe the function of the p53 tumour suppressor gene

Answer 25

P53 is a transcriptional factor that can activate the p21 gene

P21 protein inhibits cyclin/cdk function

Hence removal of p53 removed inhibition of cell growth

Question 26

In what % of cancers is the p53 gene mutated

Answer 26

70%

Wow

Question 27

What is the p53 upregulated modulator of apoptosis(PUMA)
akaBcl-2-binding component 3(BBC3),
-what is it 
-regulation 
-activation/action

Answer 27

pro-apoptoticprotein, member of theBcl-2protein family encoded by theBBC3gene

The expression of PUMA is regulated by the tumor suppressorp53. PUMA is involved inp53-dependent and -independent apoptosisinduced by a variety of signals, and is regulated bytranscription factors

After activation, PUMA interacts with antiapoptoticBcl-2family members, thus freeingBaxand/orBakwhich are then able to signalapoptosisto themitochondria.