Cancer Biodiversity Flashcards
“growth in the absence of stimulus” defines what?
Neoplasia.
Carcinogenesis describes the process by which a group of neoplastic cells of monoclonal origin accumulate genetic chances until a metastatic phenotype is reached.
Carcinogenesis describes the process by which a group of neoplastic cells of monoclonal origin accumulate genetic chances until a metastatic phenotype is reached.
“Well differentiated” means
cell have differentiated correctly and so they look and behave like surrounding tissue.
What is a defining feature of early G1?
Mitogen-dependent. Won’t progress without growth signals.
What do we call the point where mitogens are no longer required, and borders the early and late G1 phases?
R point
What cyclin is dominant in early G1?
Cyclin D (and CDK4,6)
What’s that concept for when both alleles need to mutate to become carcinogenic?
The KNUDSON two-hit hypothesis.
What is the relationship between active cyclin:CDK complexes, RB and E2F?
E2F mediates S-phase gene transcription.
Constitutively it is inhibited (bound) by the RB protein, which is active in its hypophosphorylated state.
Cyclin/CDK complexes phosphorylate RB, liberating E2F and progressing toward the S phase.
What is the first cell cycle checkpoint?
G1/S - checking integrity before replication.
What happens in the S phase?
DNA replication
Is p53 important in the G1/S or the G2/M checkpoint?
Trick: BOTH.
The G2/M checkpoint: checking ______
for DNA damage in replicated DNA prior to mitosis.
What do Raf and CDKs have in common?
They’re both Ser-Thr kinases.
Not to be confused with Ras, a regulatory GTPase.
Apoptosis can be pathological or physiological. How does that contrast with necrosis?
Necrosis is ONLY pathological.
What kicks necrosis off?
Some irreversible injury like ischaemia, which compromises membrane integrity.
What are 4 apoptosis triggers?
DNA beyond repair
Disfunctional proteins
Loss of BM adhesion
Immune-mediated apoptosis
Apoptosis is important to ____________.
Homeostasis of total cell population.
How does breakdown occur in apoptosis? Two important features.
- ATP dependent degradation;
2. Blebbing into apoptotic bodies for phagocytic clearance.
There are two pathways to apoptosis. What is the common feature in both of them?
CASPASE activation.
What are the two pathways of apoptosis?
Intrinsic - mitochondrial
Extrinsic - death-receptor (e.g. Fas, the TNF receptor)
What triggers intrinsic apoptosis?
Cytochrome C leakage from damaged mitochondria triggers caspase activation.
What three processes describe the disordered breakdown of DNA in necrosis?
I lied to Clancy; I didn’t put a hex on you to force you to pick your nose.
pyknosis, karyorrhexia, karolysis
What three processes describe the disordered breakdown of DNA in necrosis?
pyknosis, karyorrhexia, karyolysis
Apoptotic DNA degradation: chr_________ c_________ followed by _________ into __________ and ______ away.
Chromatin condensation and fragmentation into portions and blebbing away in apoptotic bodies.
What two words describe necrosis as a whole process under the microscope?
Swelling and rupture.
What does apoptosis look like under the microscope?
4 aspects.
nuclear shrinkage
chromatin condensation
membrane integrity preserved
blebbing into apoptotic bodies.
Describe degradation in necrosis?
Rupture and leaking of contents or enzymatic degradation.
Ultimately what triggers necrotic cell death?
ATP depletion and Ca2+ influx.
Name the six aspect headings of Apoptosis/Necrosis differences.
Process (physiological?) Mechanism/trigger Degradation and dispersal Inflammation? Microscope appearance DNA degradation mechanism
p53 is pro-apoptotic, an example of an antiapoptotic protein would be ____
BCL2
Contact inhitition is a _____ ______ ______
self-regulatory function.
Name 8 cancer hallmarks
I can’t get on the phone to Ms Hewitt - she’s gonna help me invase this castle when I can find the philosphophers stone. Once I have that I won’t need anyone’s help. I can avoid any fear of death. I promise I won’t go crazy.
Immortality Loss of contact inhibition Tissue invasion/metastasis Genomic instability Angiogenesis Growth factor self-sufficiency Poor differentiation (and pleiomorphism) Evasion of apoptosis.
Growth suppressor evasion
Immune evasion
What process is overcome to achieve immortality?
p53 can sense shortened telomeres and halt cell cycle. This doesn’t happen in cancer.
How might cancer overcome telomere-related senescence?
Ectopic activation of stem cell telomerases (which lengthen telomeres)
What are three methods a cancer can become self-sufficient from growth factors?
- constitutively active GF receptors.
- autocrine GF expression
- overexpression of receptors
What are two growth factor receptors famously overexpressed in cancer?
HER2
EGFR
What must a cell be able to do to be metastatic?
De-adhere from other cells and migrate through the basement membrane.
What is 1) the molecular and 2) the microscopic hallmarks of a ‘mutator’ phenotype?
checkpoint dysregulation
abnormal karyotype
List 6 cancer risk factors
Diet Viral infection UV radiation ionising radiation cigarette smoke environmental pollution
Asbestos
List 3 work-related carcinogens
Cadmium
Aromatic amines - RUBBER workers, DYE workers - bladder
polycyclic hydrocarbons - COAL GAS workers - skin/lung
Aromatic amines. Who’s job is risky?
Rubber and dye workers
Polycyclic hydrocarbons. Who’s problem?
Coal gas manufacturers.
List two non-genetically based risk factors for cancer susceptibility
AGE and GEOGRAPHY
e.g. melanoma in australia
What do coal gas manufacturers need to watch out for?
polycyclic hydrocarbons.
PHRASES loss-of-function; gain-of-function; loss-of-inhibition
augmentation of endogenous function
PHRASES proteins whose activities counteract the hallmarks of cancer, generally related to the cell cycle and cell death.
qualitative or quantitative changes
PHRASES inhibit neoplastic growth; constitutive activation
GF, GFr, signal transducers and transcription factors
Oncogenes ___ ___ ___ or ___ ___ ___
stimulate cell division or prevent cell death
NB Oncogene vs proto-oncogene
NB Oncogene vs proto-oncogene
Unmutated endogenous version
Inheretence patterns:
Oncogenes
TS genes
autosomal dominant
autosomal recessive
List three growth factor receptors
RET, EGFR, HER2
Transcription factor oncogene
Myc
Two ser-thr kinases (oncogenes)
CDKs; Raf
Three signal transducing oncogenes
Ras;
PI3K
Atk
What’s a GF oncogene?
Gene for PDGF platelet derived growth factor
Five TS genes
BRCA1 BRCA2 PTEN RB P53
Five non-cancer functions. p53 will have a role in them because p53 has a role in damn well everything.
cell cycle apoptosis checkpoints senescent Genome integrity
In order, the type of cell as it progresses through teh carcinogenesis stages.
- normal cell
- cell with stem cell like properties
- mutator phenotype
- cancer cell monoclonal founder
Put the four stages of carcinogenesis in order
- Initiating mutation
- Aquisitoin of genetic instability
- Acquisition of cancer hallmarks
- Further genetic evolution
_____ are constitutively expressed and are activated by ______, which aren’t constitutively expressed.
CDK; cyclins
