Cancer, breast cancer

Question 1

why is cancer the natural and inevitable end state of all multicellular organisms

Answer 1

all proliferation ic under genetic control

mutations will arise that give a cell proliferative advantage, daughter cells will take over- cancer

Question 2

what 6 capabilities must the cancer cell have to be successful

Answer 2

independent of external growth signals
insensitive to external anti growth signals
avoid apoptosis
capable of indefinite replication (avoid senescense)
of sustained angiogenesis (blood vessels grow into tumour)
capable of tissue invasion and metastasis

Question 3

if cancer is inevitable end state, why does it take us so long to get cancer

Answer 3

cancer must overcome 4-7 successive defences to convert normal cell to malignant cell, statistical chance of it very small

Question 4

what type of mutations for successful cardiogenesis

Answer 4

mutations that increase rate cell proliferation so there is an expanded target for subsequent mutations

or

mutations that destabilise genome so increases subsequent mutation rate

Question 5

familial vs sporadic cancer

Answer 5

sporadic cancer
usually exposure to environmental factors
somatic genetic alterations
99% cancers

familial cancers
siginificant inherited predisposition
mendelian inheritance
most due to inherited mutated tumour suppressor gene
rare 1%
syndromic (often assoc w other features)
h/e, inherit a predisposition to cancer not cancer itself

Question 6

proto-oncogenes and oncogenes

Answer 6

proto-oncogenes normally promote cell division, survival and growth. capable of being an excellent cancer cell hence proto oncogene

protein function is increased by mutation, dominant phenotype so only requires one allele to be activated

therefore increases rate of proliferation so chance of mutation increases

eg Her2

Question 7

what cells are proto-oncogenes and how become an oncogene

Answer 7

growth factor gene, cell surface receptor gene, 2ndry cell messenger or cell cycle machinery genes

fool receptor into thinking there is a growth factor present
chromosomal translocation to an active site so upregulated expression
chromosomal translocation to create a chimaeric gene (novel gene) encodes for overgrowth

Question 8

tumour suppressor genes, inactivation and mutation

Answer 8

normally act as breaks, tumour repair genes-
antiproliferative
pro-apoptopic
DNA repair and genome instability

may be inactivated by:
mutations
chromosomal abnorms
methylation of promoters
interaction with viral proteins

both copies of gene need to be mutated so recessive phenotype. cause loss of function

Question 9

TSG mutation familial vs sporadic

Answer 9

familial- inherit 1 mutant copy and 1 later mutates and inactivates

sporadic- both mutate randomly. 1st in 1 cell then in a daughter cell of the 1st cell (2 hit hypothesis)

Question 10

oncogenes vs tumour suppressor genes in cancer

Answer 10

oncogenes

• one copy mutated
• gain in function
• accelerates cell growth

tumour suppressive gene

• both copies gene must be mutated
• loss of function
• cannot inhibit cancer growth anymore

Question 11

normal cell cycle

Answer 11

interphase:
G0 quiescence- differentiated cells sit here, most can't reenter
G1 growth 
S DNA synthesis
G2 growth

Mitosis and cytokinesis

Question 12

how is cell progression from G2 to mitosis

Answer 12

cyclin B accumulates in G2