Lecture 16 Flashcards
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
Oncogenes
oncogenes are cancer-causing genes (mutated form of gene)
proto-oncogenes are the corresponding normal cellular genes that are responsible for normal cell growth and division
conversion of a proto-oncogene to an oncogene can lead to abnormal stimulation of the cell cycle
Conversion of proto-oncogenes to oncogenes
movement of DNA within the genome: if it ends up near an active promoter, transcription may increase
amplification of a proto-oncogenes: increases the number of copies of the gene
point mutations in the proton-oncogene or its control elements: cause an increase in gene expression
RAS
is a protein that is implicated in many types of cancer. a point mutation in RAS cam make ir permenantly active, even when the original growth factor molecule is not present (RED)
this sends a constant signal to the nucleus to constantly divide- this is cancer
Tumour suppressor genes
tumour supressor genes help prevent uncontrolled cell growth
mutations prevent transcription of tumour-suppressor genes- may contribute to cancer onset
Functions of normal tumour-suppressor genes
repair of damaged DNA (stopping mutations from being copies)
control of cell adhesion (attachment to underlying surface)
inhibition of the cell cycle in the cell-signalling pathway (stops damaged cells from replicating)
TS genes and cancer
suppression of the cell cycle can be important in the case of damage to a cells DNA: p53 normally prevents a cell from passing on mutations due to DNA damage
however, mutations in the p53 gene prevents suppression of the cell cycle-allowing damaged cells to continue to be replicated resulting in further mutations
The multistep model of cancer development
multiple mutations are generally needed for full-fledged cancer: thus the incidence increases with age
at the DNA level, a cancerous cell is usually characterised by at least one active oncogene and the mutation of several tumour suppressor genes
The multistep model of cancer development
steps
- mutation in APC gene causes loss of tumour-suppressor function (APC- adenomatous polyposis coli)
- small, benign polyp begins to grow then a mutation occurs in RAS oncogene
- followed by another mutation, this time in TS gene, DCC (deleted in colorectal cancer)
- the next mutation could be in TS gene
- then further mutations occur as the surveillance and repair function of p53 are now removed
- these mutations take years to acquire and are often symptomless in the early stages
Other factors contributing to cancer
individuals can inherit mutant alleles of tumour-suppressor or oncogenes
inherited mutation are common in colorectal cancer
treatment can be precautionary
