1. Cancer cells have lost genetic controls on cell division and are immortal, metastasizing and spreading to other tissues. They have also lost differentiation. 2. The cell cycle is tightly regulated by internal and external signals at checkpoints like G1 to control division. Cancer cells evade these controls. 3. Oncogenes are mutated genes that cause uncontrolled growth, while tumor suppressor genes normally stop division but are inactivated in cancer.

1. 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
 Cancer is heritable—Cancer cells give rise to cancer
cells
2. Immortal
3. Not subject to contact inhibition
4. Metastasize: Spread into other tissues
5. Are Dedifferentiated
 less specialized than the cell it came from)

2. 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.

3. EXPERIMENT
RESULTS
Figure 12.14
Evidence that Cytoplasmic Signals Control the cell Cycle

4. Mitosis:
division of
the nucleus
Cytokinesis:
division of
cytoplasm
Daughter
cells
M-phase
Interphase =
G1, S, G2
S-phase
G2-phase G1-phase
Prep.
for division:
organelles
duplicate
Cell growth +
normal cell
activities
Synthesis of DNA
(chromosomes replicate)
Cells
divide
The Cell Cycle

5. 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

6. • 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.
The Cell Cycle Control System

7. 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?

8. 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

9. • 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.
External Signals at the Checkpoints

10. Figure 12.19
Anchorage dependence
Density-dependent inhibition (Contact Inhibition)
Density-dependent inhibition
(a) Normal mammalian cells (b) Cancer cells
20 m 20 m

11. 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.

12. 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?

13. 1. Normal cell growth 2. Basal cell carcinoma
Both daughter
cells divide
Actively dividing cells
(basal cells)
Only one daughter
Cell divides
One
daughter
differentiat
es

14. 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 enters
S-phase and divides,
eventually repairing
wound
target cell
Nucleus

15. 1. Cell might
produce
its own
growth
factor
Several ways to get faulty growth control in a cancer cell
2. Mutant receptor might turn
on even without
binding 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

16. 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.

17. 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?

18. 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?

19. 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?

20. 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?

21. Figure 12.20
Glandular
tissue
Tumor
Lymph
vessel
Blood
vessel
Cancer
cell
Metastatic
tumor
A tumor grows
from a single
cancer cell.
Cancer
cells invade
neighboring
tissue.
Cancer cells spread
through lymph and
blood vessels to
other parts of the
body.
Cancer cells
may survive
and establish
a new tumor
in another part
of the body.
4
3
2
1
The growth and metastasis of a malignant breast tumor

22. 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.

23. 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)

24. Phase-specific Chemotherapies
1. Prevent cells from entering the S-phase
» Block Growth factor receptors on cell membrane
with antibody (e.g. Herceptin)
2. Block the S phase
» Thioguanine and Methotrexate and other
chemotherapeutic drugs block DNA synthesis
3. Block or stop mitosis
» Taxol: interferes with the movement of the
chromosomes along spindle fibers

25. 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?

26. 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

27. 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

28. 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