Tumour pathology 4+5 Flashcards
Mitotic division creates…
2 genetically identical daughter cells
define ‘cell cycle’
time interval between mitotic divisions
mitosis
Mechanism of cellular replication
nuclear division plus cytokinesis
Normal cell cycle phases
during interphase:-
G1, S, G2, M
G1 is the first growth stage- cell makes new proteins and copies of the organelles.
S phase is when DNA replication occurs
G2 is 2nd period of cell growth- more proteins and copies of organells in prep for mitosis.
M is mitosis and cytokinesis
G0 phase of cell cycle
G1 checkpoint- cell is checked for cell size- sufficient cell mass is needed to form two daughter cells. If go ahead is not reached cell may switch to a non-dividing state called G0 phase. Can return to cycle if conditions change
What is the ‘cell cycle’
Ordered series of events between mitotic divisions. Has to be highly regulated because can lead to degenerative diseases or cancer.
A cell must progress through cycle phases…
in the correct sequence in order to produce viable progeny (new cells)
Cell cycle checkpoints
if cell size is inadequate= G1 or G2 arrest
if nutrient supply is inadequate= G1 arrest
If DNA is not replicated= S arrest
chromosome mis-alignment= M-phase arrest
How must DNA synthesis and mitosis occur?
sequentially
External control of cell cycle
Hormones, growth factors, cytokines
Intrinsic factors
critical checkpoints
prior to G1 checkpoint- progress through was due to external factors and after it is autonomous
Carcinogenesis
the initiation of cancer formation. It is caused by mutation of genetic material that upsets the normal balance between proliferation and apoptosis
List the major aetiologies (causing) of cancer
uncontrolled proliferation of cells via cell cycle dysregulation
disruption of the cyclin D-pRb-E2F pathway
disruption of the p53 pathway ( two regulatory pathways)
environmental changes (chemicals, radiation, oncogenic viruses)
inherited
uncontrolled proliferation of cells effect
increased rate of cell cycle may result in tumour formation
may be benign or malignant
what causes a cell to lose control of proliferation?
mutations in genes regulation cell division, apoptosis and DNA repair
Chemical carcinogenesis
Chemical carcinogens or their active metabolites react with DNA forming covalently bound products (DNA adducts)
Adduct formation at particular chromosome sites causes cancer
Radiation carcinogenesis
High-energy radiation is carcinogenic if received in sufficient doses
ultraviolet radiation (UV-B present in sunlight)
X-rays
Gamma radiation
Abnormal cell cycle
The primary defect in cancer is –
Uncontrolled cell proliferation via cell cycle dysregulation
Absent or inactive pRb…?
releases the cell cycle brake- leading to over- proliferation
p53 protein
important part of G1 checkpoint
transcription factor
can stimulate DNA repair, arrest the cell cycle or trigger cell death
important point about tumour formation is that it is
a multi-step process
key event in tumour formation is?
uncontrolled cell proliferation via cell cycle dysregulation via loss of tumour suppressor gene function
Carcinogenesis:- heredity?
inherited cancer syndromes
familial cancers
autosomal recessive syndromes of defective DNA repair
Evidence of a tumour in malignancy means absence of what?
a capsule
name 2 breast cancer tumour suppressor genes?
BRAC1 BRAC2
