I. The cell cycle and cell division processes differ between prokaryotic and eukaryotic cells. Loss of control over the cell cycle can lead to cancer. Key control points include checkpoints in G1, G2, and metaphase.
II. The cell cycle is regulated by cyclins and cyclin-dependent kinases (Cdks) that control progression through the phases. Mutations in genes that control cell growth, division, and death can lead to uncontrolled cell growth and cancer.
III. Environmental factors like radiation, toxins, and chemicals can damage DNA and cause mutations in control genes, increasing cancer risk over time. Lifestyle choices around sun exposure, smoking, diet, and early detection
The Cell Cycle and Cancer Control: A Guide to Cell Growth, Division, and Death
1. The cell cycle
prokaryotic
eukaryotic
Control of the cell cycle
loss of control- cancer
What is cell differentiation and why does it happen?
what is a stem cell?
What is cloning?
implications of cloning
2. Cell division
prokaryotes- binary fission
one bacterium divides into two
one circular chromosome replicates
beforehand
two identical daughter cells form
can take as little as 15 minutes
eukaryotes
DNA is replicated before cell division
somatic cells- mitosis
two identical daughter cells
germ cells- meiosis
gametes (sperm and eggs) which
fuse to form a zygote
takes much longer
3.
4. Eukaryotic cells have several chromosomes
Number varies among species (p. 138)
humans have 46 (23 pairs)
diploid organisms have pairs of
chromosomes
chromosome structure is complex
How much of that chromosome actually contains
genetic information?
5.
6.
7. How long does the cell cycle last?
Depends on the cell
stem cells, embryonic cells- a few hours
(embryonic cells don’t really have G1 and
G2- why?)
Some cells divide very slowly
Some cells divide when induced
liver
lymphocytes
8. Cell division
Cells grow during interphase
DNA is replicated during S phase
Division of nucleus during M phase (mitosis)
Division of cytoplasm (cytokinesis)
Programmed cell death (apoptosis)
Cells divide only a certain number of times
and then die (Hayflick limit)
Role of telomeres?
9. Control of cell cycle- by special proteins and
enzymes that act as switches
G1 checkpoint- stop, pause or go into S phase
some cells stop permanently
G2 checkpoint- will cell divide?
M checkpoint- formation of new cells
10. Early 1970s
M phase drives G1 cell into mitosis, even though
S phase has not occurred
S + G1: G1 cell starts S phase
S phase + G2: G2 will not undergo DNA synthesis
11. I. G1 varies the most among cell types
first of several checkpoints is seen
What determines whether a cell will grow?
Single-celled organisms grow if enough nutrients
are present
Multicellular organisms must grow in a controlled
way: growth factors
Mitogens stimulate cells to go into S phase
12. Many growth factors have been described
how do they work?
Bind to tyrosine kinase receptors
Activate Ras pathway (a small membrane G
protein)
↓
Cascade of phosphorylation reactions, followed
by transcription
Cell passes into S phase
13. II. G2 checkpoint (between G2 and M)
DNA synthesis must be complete and correct
Cell may be arrested at this point
This checkpoint tends to be more important
in certain types of cells, e.g., fertilized
frog eggs and certain strains of yeast
14. Cyclin-dependent kinases (Cdk)
first discovered in yeast
Different kinds of cyclins; levels oscillate at
different stages of cycle
Control mechanisms
availability of cyclins varies
Cdk must be phosphorylated
Cyclin and Cdk must be bound together to be
active
15. Initial cyclin-Cdk complex is inactive
a series of phosphorylation and dephos-
phorylation steps make it active
Complex is called MPF (mitosis-promoting
factor)
Present in both mitosis and meiosis
highly conserved
17. G1 checkpoints
Rb prevents cell moving into S phase by binding
to a transcription factor
When Rb is phoshporylated it cannot bind so
cell can move into S phase
p53 prevents damaged from dividing (by inhibiting
Rb pathway)
Abnormalities in both genes are associated with
hereditary forms of cancer
18. III. Spindle assembly checkpoint, between
metaphase and anaphase
Cell cycle can be arrested if spindle fibers are
not attached properly to chromatids
19.
20. Cell growth is usually tightly regulated
Controls:
contact inhibition- cells will grow to a
certain density
finite number of cell divisions
“gatekeeper genes”
proto-oncogenes- stimulate growth
some make growth factors
some respond to growth factors
21. Types of proto-oncogenes
Growth factors
Receptors (G protein and tyrosine kinase)
Kinases
Transcription factors
Cdk-kinases
Mutant forms, oncogenes that promote cancer,
have been identified in every category
22. Tumor suppressors- inhibit cell growth
Cancers occur when cells grow out of control
invade and damage tissues
cells themselves may not function
properly
How does this happen? Mutations accumulate
in DNA
23. If mutations occur in control genes, they can’t
regulate cell growth
Some defects in particular genes are associated
with specific cancers
BRCA-1 tumor suppressor gene associated with
some inherited breast cancers
p53- tumor suppressor- associated with many
colon, bladder, breast, brain, lung cancers
(about half of all cancers!)
24.
25. What about this “cell destruction”?
Damaged cell undergoes apoptosis
(programmed cell death)
Genetically regulated- cell has genes that both
promote and inhibit death
How does programmed cell death differ from
death by injury?
26.
27. Inheritance of “cancer gene”:
Each cell has 2 copies of p53. If both become
damaged, they lose control of cell growth
If you inherit one “damaged” copy, you’re
halfway there!
Mutations occur over time- cancer is more
common in older people
Most cancer is NOT inherited; environmental
damage causes most cancer
28. What sorts of things cause this damage?
Radiation
Toxins
Chemicals
Our bodies have many processes that repair
damaged DNA
29. Avoid sun exposure
Avoid smoking
Eat moderately; consume fiber. Some foods
may help prevent cancer?
Early detection (especially important if you
have a family history of cancer)
30. As more is known about mechanisms of
uncontrolled cell growth, new treatment
strategies will emerge
Radiation
Chemotherapy
Immunotherapy
Kinase inhibitors
Angiogenesis inhibitors
Gene replacement