Lecture 16 Flashcards
(33 cards)
Cell cycle control
the frequency of division varies with the type of cell
the cell cycle differences result from regulation at the molecular level
Stages of cell cycle
G1: 1st growth 4-6 hours
S: synthesis (DNA replication) 10-12 hours
G2: 2nd growth 5-6 hours
M: Mitosis 1 hour
The cell cycle control system
the sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock
the cell cycle control system is regulated by both internal and external controls
The clock has specific checkpoints where the cell cycle stops until a g-ahead signal is received
G1 checkpoint
seemingly the most important
if a cell receives a Goa-head signal at ehe G1 checkpoint, it will usually complete the S, G2 and M phases and divide
if the cell doesn’t receive this signal it will exit the cycle, switching into a non-dividing state called the G0 phase (inactive)
G2
preparing for mitosis phase
synthesising more organelle
S phase
synthesising mRNA, proteins (histones), DNA polymerase
G0 phase
viewed as either an extended G1 phase where the cell is neither dividing nor preparing to divide
or
a distinct quiescent stage that occurs outside of the cell cycle
Two main regulatory proteins
cyclin-dependent kinase
cyclins
Cyclin-dependent kinase
-levels of kinase are constant throughout cell cycle but mostly inactive
-kinase must bind o a cyclin to become activated
Cyclins
levels of cyclin fluctuate throughout the cell cycle
activity of CdK is controlled by the levels of cyclin present
the first cyclin-CdK complex discovered was called MPF
(maturation promoting factor)
Fluctuation of MPF activity and cyclin concentration
when MPF is active, it phosphorylated other proteins, which triggers for example:
-fragmentation of the nuclear envelop (by depolymerisation of lamins)
-mitotic spindle formation (by polymerisation of tubulin into microtubules
Stop and Go signs
internal and external signals at the checkpoints
e.g- kinetochores not attached to spindle microtubule send a molecular signal that delays anaphase
some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide
Platelet-derived growth factor (PDGF)
cell growth required the presence of PDGF
stimulate the division of human fibroblasts cells in cell culture
PDGF experiment
a sample of human tissue is cut up
enzymes are used to digest the connective tissue, leaving the free fibroblasts
cells are transferred to culture dish and supplemented with nutrients and growth factors
when growing normal cells in culture in the lab, the growth factor PDGF must be added to the medium, otherwise the cells will not grow
External signals
another example of external signals is density-dependant inhibition, in which crowded cells, stop dividing
most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum (underlying layer) in order to divide
Anchorage dependance
cells anchor to the bottom of the dish
Density dependent inhibition
it has been observed in the labs that cultured cells will grow and spread out until they form a single layer of cells-then they stop dividing
if cells are scraped away the others will grow to fill the gap then stop again
Normal mammalian cells growth
contact with neighbouring cells and the availability of nutrients, growth factors and the attachment to a surface ALL limit cell density to a single layer
Cancer cell growth
these cells divide well beyond a single layer, forming a clump of overlapping cells, they do not display anchorage-dependance or density dependent inhibition
Loss of cell cycle controls in cancer cells
cancer cells do not respond normally to the bodys control mechanisms
they divide excessively and invade other tissues
cancer cells may not need growth factors to grow and divide
- they may make their own growth factor
-they may convey a growth factor signal without presence of growth factor
-they may have an abnormal cell cycle control system
What is cancer
a normal cell is converted to a cancerous cell by a process called transformation
the immune system should usually recognise and destroy this cell but the cell can sometimes evade destruction
the transformed cells grow to form tumours: masses of abnormal cells within otherwise normal tissue
if abnormal cells remain at the original site, the lump is called a benign tumour
malignant tumours invade surrounding tissues and can metastasise exporting cancer cells to other parts of the body where they may form secondary tumours
Growth and metastasis of a malignant breast tumour
- a tumour grows from a single cancer cell
2.cancer cells invade neighbouring tissue
3.cancer cells spread through lymph and blood vessels to other parts of the body - a small % of cancer cells may survive and establish a new tumour in another part of the body
Genetic changes that affect the cell cycle
the gene regulation systems that go wrong during cancer are the same systems involved in embryonic development and normal growth
- growth factors (ligands)
- membrane receptors
- and signal transduction proteins
cancer can be caused by mutations I genes that regulate cell growth and division, DNA repair and apoptosis
Two types of genes associated with cancer
oncogenes
tumour supressor genes
