Lecture 16

Question 1

Cell cycle control

Answer 1

the frequency of division varies with the type of cell

the cell cycle differences result from regulation at the molecular level

Question 2

Stages of cell cycle

Answer 2

G1: 1st growth 4-6 hours
S: synthesis (DNA replication) 10-12 hours
G2: 2nd growth 5-6 hours
M: Mitosis 1 hour

Question 3

The cell cycle control system

Answer 3

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

Question 4

G1 checkpoint

Answer 4

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)

Question 5

G2

Answer 5

preparing for mitosis phase

synthesising more organelle

Question 6

S phase

Answer 6

synthesising mRNA, proteins (histones), DNA polymerase

Question 7

G0 phase

Answer 7

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

Question 8

Two main regulatory proteins

Answer 8

cyclin-dependent kinase

cyclins

Question 9

Cyclin-dependent kinase

Answer 9

-levels of kinase are constant throughout cell cycle but mostly inactive
-kinase must bind o a cyclin to become activated

Question 10

Cyclins

Answer 10

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)

Question 11

Fluctuation of MPF activity and cyclin concentration

Answer 11

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

Question 12

Stop and Go signs

Answer 12

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

Question 13

Platelet-derived growth factor (PDGF)

Answer 13

cell growth required the presence of PDGF

stimulate the division of human fibroblasts cells in cell culture

Question 14

PDGF experiment

Answer 14

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

Question 15

External signals

Answer 15

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

Question 16

Anchorage dependance

Answer 16

cells anchor to the bottom of the dish

Question 17

Density dependent inhibition

Answer 17

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

Question 18

Normal mammalian cells growth

Answer 18

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

Question 19

Cancer cell growth

Answer 19

these cells divide well beyond a single layer, forming a clump of overlapping cells, they do not display anchorage-dependance or density dependent inhibition

Question 20

Loss of cell cycle controls in cancer cells

Answer 20

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

Question 21

What is cancer

Answer 21

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

Question 22

Growth and metastasis of a malignant breast tumour

Answer 22

1. 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
2. a small % of cancer cells may survive and establish a new tumour in another part of the body

Question 23

Genetic changes that affect the cell cycle

Answer 23

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

Question 24

Two types of genes associated with cancer

Answer 24

oncogenes

tumour supressor genes

Question 25

Oncogenes

Answer 25

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

Question 26

Conversion of proto-oncogenes to oncogenes

Answer 26

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

Question 27

RAS

Answer 27

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

Question 28

Tumour suppressor genes

Answer 28

tumour supressor genes help prevent uncontrolled cell growth

mutations prevent transcription of tumour-suppressor genes- may contribute to cancer onset

Question 29

Functions of normal tumour-suppressor genes

Answer 29

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)

Question 30

TS genes and cancer

Answer 30

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

Question 31

The multistep model of cancer development

Answer 31

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

Question 32

The multistep model of cancer development
steps

Answer 32

1. mutation in APC gene causes loss of tumour-suppressor function (APC- adenomatous polyposis coli)
2. small, benign polyp begins to grow then a mutation occurs in RAS oncogene
3. followed by another mutation, this time in TS gene, DCC (deleted in colorectal cancer)
4. the next mutation could be in TS gene
5. then further mutations occur as the surveillance and repair function of p53 are now removed
6. these mutations take years to acquire and are often symptomless in the early stages

Question 33

Other factors contributing to cancer

Answer 33

individuals can inherit mutant alleles of tumour-suppressor or oncogenes

inherited mutation are common in colorectal cancer

treatment can be precautionary