Cancer cells and meiosis Flashcards
size of organ depends on total cell mass dependent o
total number of cells and their size
processes regulated
cell growth, cell division, cell survival
by intracellular programmes and extracellular signal molecules
3 external factors to reach cell from outside - affects progression of cell cycle
mitogen
growing factors
survival factors
mitogen function
stimulate cell division by triggering waves of G1/S-Cdk activity - relieves intracellular negative control
growing factor
stimulate cell growth by promoting protein synthesis and other macromolecules and inhibiting their degradation
survival factors
promote cell survival - suppressing the form of programmed cell death(apoptosis)
social control of cell
tells how cells act
from outside - extracellular signals
cancer cells
cells that no longer respond to social signals
cancer progression
evolutionary process driven by gene mutation(providing cell with competitive advantage)
mechanism of mutated cells
suppresses mechanism of apoptosis
evolution of cancer
initial clone of cancerous cells - additional mutation increase causing generation of diverse sub clones forming cancer cells
Hall marks of cancer cells
organising principles of rationalising complexities of neoplastic disease
hall marks includes
sustaining proliferative signalling, evading growth suppressors etc
hallmarks genome instability
generates genetic diversity that expedites acquisition, inflammation which fosters multiple hallmark functions
features of cancer cells of mutation
- display altered control growth
- contain and accumulate somatic mutation
- single mutation - not enough to change normal cells into cancerous cell
have abnormal to survive stress and DNA damage - create own microenvironment(niche) - evolve
feature of cancer cells of control and spread
- can bypass normal proliferation control - independence of mitogens
- colonise other tissues
- develop gradually from increasingly aberrant cells
- altered sugar metabolism
- genetically unstable
2 genes where mutation stimulates tumour progression
oncogene and tumour suppressor gene
oncogene
act in dominant manner
gain of function
oncogene function
promote cancer - protooncogene - overactive/overproduced
- regulate cell growth, division, survival or differentiation
tumour suppressor gene function
normally restrain cell proliferation or tumour - loss of gene increases causing cancer formation
example of oncogene
activation via mitogen stimulation
process of activation via mitogen stimulation
- mitogens bind to cell surface receptor = initiate intracellular signalling pathway
- activation of small GTPas.Ra which activates MAP kinase cascade, increasing expression of numerous intermediate early genes including gene encoding transcription regulatory protein Myc
Myc in example of oncogene
increase expression of delayed response gene expression which increases G1-Cdk activity which triggers phosphorylation of Rb family of protein
inactivation of Rb proteins
freeing gene regulatory protein E2F
activating G1/S gene transcription including genes for G1/S-cyclin and S-cyclin
activating G1/S gene transcription
enhances Rb protein phosphorylation = positive feedback loop
E2F protein stimulate transcription of their genes after Rb protein phosphorylation
positive feedback loop formed as well
tumour suppressor gene
actin submissive manner
loos of function
defects that contribute to cancer
signalling pathways
cell cycle control
apoptosis regulation
example of tumour suppressor
p53 - cellular stress sensor
p53 function
responds to hyper-proliferation signals, DNA damage, hypoxia, telomere shortening and various stresses
mutation of p53
enables cancer cells to survive and proliferate despite stress and DNA damage
even with DNA damage the cell cycle will continue = cancer as cell cycle cannot be arrested
cell cycle is mis regulated in multiple cancers
change in genes which encodes cell cycle regulator - identified in human cancer cells
most cancers have unstable genomes
genetic (genomic) instability chromosomal instability (CIN)
genetic (genomic) instability
abnormal increases in rate at which genes and chromosomes are mutated, rearranged or lost
chromosomal instability (CIN)
abnormally high incidence of defects in chromosome number of chromosome structure
meiosis
nuclear division leading to generation of haploid cells
in gametes
many control systems and molecular mechanisms are shared with mitotic division
meiosis I
time taken longer than meiosis II especially prophase
homologous chromosome recognise each other and associate
meiosis I structure
2 closely aligned duplicate homologs - bivalent
meiosis I - synaptonemal complex (SC)
protein complex usually joining to homologs
prophase I stages
leptotene, zygotene, pachytene, diplotene
leptonene
homologous chromosomes condense partially, pair and genetic recombination begin
sygotene
SC start to assemble; synapsis and recombination are taking place
pachytene
SC complete and recombination finishes are very tightly linked
diplotene
disassembly of SC, condensation and shortening of chromosomes
after chiasmata are visible
homologies can segragate
SC
each homolog is organised around protein axial core and SC form when these homolog axes are linked by rod shaped transverse filaments
axial cores of each homolog
interacts with cohesin complexes that hold the sister chromatids together
location of SC
between sister chromatid especially during crossover
uses cohesin
homolog synapsis and desynapsis during different stage of prophase
2 sister chromatids coalesce and chromatid loops extend out from common axial core
assembly of synaptonemal complex begins
in early zygotene and complete in pachytene
complex disassembles in diplotene
SC under electron microscope
from meiotic cell at pachytene in lily flower
cross over
chiasmata
chiasmata
crossover seen as thin connection between homologs
chiasmata in late stage bivalent
single crossover occurs between non sister chromatids
when SC disassembles and separate a little at end of prophase I
difference in meiosis I to mitosis
- both sister kinetochores remain attached to same spindle pole
- chiasmata keep homologs together which allows bi-orientation
- centromeric cohesin on sister chromatid remains bound through anaphase
