Transcript Mitosis/Cancer Lecture Notes

Characteristics of Cancer Cells
•
Obituary brings to light the tragedy of one local
family (at ALE section of Website)
Characteristics of Cancer Cells…
1. Have lost the genetic ability to stop dividing

2.
3.
4.
5.
Cancer is heritable—Cancer cells give rise to cancer
cells
Immortal
Not subject to contact inhibition
Metastasize: Spread into other tissues
Are Dedifferentiated

less specialized than the cell it came from)
The eukaryotic cell cycle is regulated by a
molecular control system
• The frequency of cell division varies with the type
of cell
• These differences result from regulation at the
molecular level
• Cancer cells manage to escape the usual controls
on the cell cycle
© 2011 Pearson Education, Inc.
Evidence that Cytoplasmic Signals Control the cell Cycle
EXPERIMENT
RESULTS
Figure 12.14
The Cell Cycle
Mitosis:
division of
the nucleus
M-phase
G2-phase
Cytokinesis:
division of
cytoplasm
G1-phase
Cells
divide
Prep.
for division:
organelles
duplicate
Cell growth +
normal cell
activities
Synthesis of DNA
(chromosomes replicate)
Interphase =
G1, S, G2
Daughter
cells
S-phase
The Cell Cycle Control System
• is like to clock
• regulated by both
internal and external
controls
• has specific
checkpoints where
the cell cycle stops
until a go-ahead
signal is received
Figure 12.15
The Cell Cycle Control System
• For many cells, the G1 checkpoint is the most
important
• If a cell receives a go-ahead signal at the G1
checkpoint, it will usually complete the S, G2, and M
phases and divide
• If the cell does not receive the go-ahead signal, it will
exit the cycle, switching into a nondividing state
called the G0 phase
© 2011 Pearson Education, Inc.
Regulation of Cell Division

What evidence in your own life do you have
that cell division is regulated
by your body?
»
»

Left ear is about same size as right ear.
A cut your finger heals, but the skin doesn't just
keep growing!
What normally controls cell division?
Stop and Go Signs:
Internal and External Signals at the Checkpoints
• Examples of internal signals
– Errors in S-phase
• molecular signal sent that prevents cell from leaving G2
– Kinetochore does not attach to Spindle Fiber:
• molecular signal sent that delays anaphase
• An Example of an External Signal
– Growth Factors
• proteins released by certain cells that stimulate other
cells to divide
External Signals at the Checkpoints
• Density-dependent inhibition
– crowded cells stop dividing
– Also known as contact inhibition
• Anchorage dependence
– Most cells must be attached to a substratum in order
to divide
• Cancer cells
– exhibit neither density-dependent inhibition nor
anchorage dependence
© 2011 Pearson Education, Inc.
Anchorage dependence
Density-dependent inhibition (Contact Inhibition)
Density-dependent inhibition
20 m
(a) Normal mammalian cells
Figure 12.19
20 m
(b) Cancer cells
Contact Inhibition
Cells do not normally grow or divide when in
contact w/ other Cells
 E.g. Cultured cells in a petri dish

»
»

will divide until they form a layer one cell thick
and then stop when make contact w/ other cells.
Called contact inhibition of cell growth.
Cells can migrate in culture
»
Stop moving when touch other cells due to contact
inhibition of cell movement.
Contact inhibition
does not occur in Cancerous Cells

Cancerous cells continue growing and
moving when they touch other cells.
»

They pile up and they migrate to other parts of
the body -- the cancer spreads.
Growth Factors
»
»
»
made of protein
Chemical messages that control the cell cycle
How do we know the cell cycle is under genetic
control?
1. Normal cell growth
2. Basal cell carcinoma
One
daughter
differentiat
es
Only one daughter
Actively dividing cells
Cell divides
(basal cells)
Both daughter
cells divide
Role of Growth Factors in Normal Cells
Signaling cell
Growth factor
Growth factor binds to receptor
Receptor sets off a signal
cascade to nucleus
target cell
Nucleus
target cell enters
S-phase and divides,
eventually repairing
wound
Several ways to get faulty growth control in a cancer cell
2. Mutant receptor might turn
on even without
binding growth factor
1. Cell might
produce
its own
growth
factor
3. Signal cascade might
occur even without trigger
from receptor
In each case, cancer cell
enters S phase and
divides inappropriately,
causing a tumor
Growth Factors
Stimulate Cell Division
Diffuse through the body making contact
with many different cells
 Bind to Membrane Receptors, like a key
fitting into a lock.

»
stimulate a pathway inside cell that leads to cell
division.
Each receptor binds to a different growth
factor.
 Different cell types are stimulated by
different growth factors.

Cancer: It’s all in the Genes

Proto-oncogenes:
»
»
»

Genes that code for growth factors
Active in actively dividing tissues (e.g. skin)
Sometimes mutate into......
Oncogenes:
»
»
genes that cause cancer
produce too much growth factor
– Over stimulate mitosis
 Oncogenes
are rarely inherited.....Why?
Tumor Suppressor Genes
 Tumor
»
Suppressor Genes
Code for Proteins that turn off cell division
e.g. p53 gene
 p53
»
»
Gene
Codes for a protein that stops the cell cycle
after G1
Half of all cancers involve p53
 One
mutant Tumor Suppressor Gene
does not cause cancer....Why?
p53: A Tumor Suppresser Gene

How many p53 genes did you inherit? Why?

How many p53 genes need to mutate before a
cell becomes cancerous? Why?
BRCA 1:
Breast Cancer Susceptibility Gene
BRCA 1 is a Tumor Suppresser gene
 If a women inherits BRCA 1 she has a

» 80 to 90% chance of developing breast cancer
» 40 to 50% chance of ovarian cancer.
» Why aren’t the percentages 100%?

Why are the percentages much lower for the
average woman?
The growth and metastasis of a malignant breast tumor
Tumor
Lymph
vessel
Blood
vessel
Glandular
tissue
Cancer
cell
1 A tumor grows
from a single
cancer cell.
Metastatic
tumor
2 Cancer
3 Cancer cells spread
cells invade
neighboring
tissue.
through lymph and
blood vessels to
other parts of the
body.
Figure 12.20
4 Cancer cells
may survive
and establish
a new tumor
in another part
of the body.
The Role of the
Environment in Causing Cancer
Certain Viruses, toxins, or Radiation may lead
to a p53 mutation
 A 2nd p53 mutation may lead to one of the
following cancers

»
»
Cancer of the....
Bladder, blood, brain, breast, colon, esophagus,
liver, lung, spleen, thyroid, etc.
Therapeutic Strategies for
Treating Cancer
Slash – Burn – Poison!!
 Since cancer is uncontrolled cell division, all
chemotherapeutic treatments involve the cell
cycle.

» Phase-specific chemotherapies
–
–
–
Prevent cells from entering S-phase
Block the S-phase
Block the M-phase (mitosis)
Phase-specific Chemotherapies
Prevent cells from entering the S-phase
1.
»
Block Growth factor receptors on cell membrane
with antibody (e.g. Herceptin)
Block the S phase
2.
»
Thioguanine and Methotrexate and other
chemotherapeutic drugs block DNA synthesis
Block or stop mitosis
3.
»
Taxol: interferes with the movement of the
chromosomes along spindle fibers
Cells Affected by Chemotherapy
Chemo may affect all dividing cells
 Which cells divide rapidly?

»
»
»
»
Hair follicle cells
Skin cells
Cells lining digestive tract
Blood stem cells
– Divide to produce???

So.... what would be the side effects?
Side Effects of Chemotherapy
Baldness
 Cuts and wounds heal slowly
 Destroy lining of digestive tract

»

nausea and severe bacterial infection
Decrease Blood cell Production
»
»
RBC’s  Anemia
WBC’s  decreased ability to fight infections and
kill cancer cells
How to
Lower your Cancer Risks

Eat plenty of fiber
» Fiber speeds passage through digestive tract
Do not smoke
 Drink alcohol in moderation or not at all
 Exercise regularly
 Do not become overweight
 Limit dietary fat
 Limit sun exposure or use sunscreen (SPF 30)
 Learn to recognize the warning signs of cancer

Common Warning Signs of Cancer:
C.A.U.T.I.O.N.
C - change in bowel or bladder habits
A - a sore that does not heal
U - unusual bleeding or discharge
T - thickening or lump in the breast or any part
of the body
I - indigestion or difficulty swallowing
O - obvious change in a wart or mole
N - nagging cough or hoarseness