W3- Lecture 16.3- Neoplasm 3 Flashcards
What is pathogenesis ?
mechanism that causes the disease
Name the 10 hallmarks of cancer
Found by Weinberg and hanahan
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
Name the 6 hallmarks of cancer
Self sufficient growth signals Insensitive to anti-growth signals Tissue invasion and metastasis Limitless replication potential Sustained angiogenesis Evading apoptosis
What is a proto-oncogene
normal gene that can become an oncogene (cancer-producing gene) due to mutations or increased expression
Which two major classes of regulatory molecules determines a cells progression through the cell cycle
Cyclins
Cyclin-dependant kinases
How are cyclin dependant kinases activated by cyclins
Via phosphorylation
Describe growth factor signalling
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
Name 4 ways that during tumorigenesis a cell can acquire a growth advantage by self sufficiency in growth signals
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
What is an autocrine loop
Atypeofinteractionbetweengrowth factors,cytokinesandtargetcells,in which acellproducesthesamegrowth factorsandcytokinesforwhichithas receptors
Describe Platelet-derived growth factor(PDGF)
one of the numerousgrowth factors, orproteinsthat regulatecellgrowth anddivision. In particular, it plays a significant role inblood vessel formation(angiogenesis),
what are Glioblastomas?
Form of aggressive brain cancer
What is a Transforming growth factor/tumour growth factor/TGF
Used to describe two classes ofpolypeptidegrowth factors,TGFαandTGFβ.
produced inmacrophages,braincells, andkeratinocytes, and inducesepithelialdevelopment
What are sarcomas ?
are malignant tumorsmade ofcancellous bone,cartilage,fat,muscle,vascular, orhematopoietictissues
What are Fibroblast growth factors, orFGFs ?
family ofgrowth factors, with members involved inangiogenesis,wound healing.
What are Hepatocyte growth factor/scatter factor(HGF/SF)
aparacrine(cell-cell communication) cellular growth,motilityandmorphogenic factor.
In what cancers would we find
Platelet Derived GF
Tumour GFa
Fibroblast GF
Hepatocyte GF
glioblastomas (brain cancer).
sarcomas (cancers of bone/fat/cartilage origin).
melanomas
thyroid tumours
Describe the Ras oncogene
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.
How is an active Ras activated
Inactive Ras is bound to GDP and active Ras is bound to GTP.
Why does a mutation of Ras drive signal transduction
The mutation stops the inactivation of Ras so it stays active and constantly signals the dive of cell cycle
What is myc ?
+ over expression causes ?
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
Name a Transcription factor that controls cyclin expression
Myc
Where is myc oncogene over-expressed ?
breast, colon and lung carcinomas, and in Burkitt’s lymphoma.
Name one cyclin and one CDK that are often over-expressed in cancer
+ type of cancer
Cyclin d
-breast, oesophagus and liver carcinomas
CDK4
-melanomas, sarcomas and glioblastomas.
Name three cell cycle inhibitor
that when distrusted over-proliferation cell may take place
retinoblastoma protein (Rb). p53. Cdk inhibitors (eg p16, p21)
