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Mitosis & Cancer Lecture Notes
Biol 100 – K.Marr
Topics for the next few lectures


Mitosis and Cancer: Cause of Cancer + Therapies
Reading assignments in Essential Biology :



Ch 8: Cellular Basis of Repro. & Inheritance
pp. 128-129: Cancer Cells—growing out of control
pp. 211-214: The Genetic Basis of Cancer
This week’s lab activity

Lab 5: Online Karyotyping and Mitosis.
Optional further reading
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
See the Biology 100 web site for links to the articles
below and more!
Varmus, H. & R.A. Weinberg "Genes and the
Biology of Cancer" Scientific American Library 1993
"What You Need to Know About Cancer" Special
Issue of Scientific American, September 1996
Cancer Statistics
How many of us will develop cancer?
One million new cases of cancer yearly in U.S.
10 million currently being treated for cancer
1.
2.
3.

How much do you know about cancer.....?
Questions we will try to answer
1. What is cancer?
2. How are cancerous cells different
than normal cells?
3. How do you get cancer?
i.e. What makes normal cells become cancer
cells?
US Mortality, 2002
Rank
Cause of Death
No. of
deaths
% of all
deaths
1.
Heart Diseases
696,947
28.5
2.
Cancer
557,271
22.8
3.
Cerebrovascular diseases
162,672
6.7
4.
Chronic lower respiratory diseases
124,816
5.1
5.
Accidents (Unintentional injuries)
106,742
4.4
6.
Diabetes mellitus
73,249
3.0
7.
Influenza and pneumonia
65,681
2.7
8.
Alzheimer disease
58,866
2.4
Nephritis
10.
Septicemia
40,974
1.7
33,865
1.4
Source: US Mortality Public Use Data Tape 2002, National Center for Health Statistics, Centers for Disease Control
and Prevention, 2004.
Lifetime Probability of Developing Cancer,
By Site, Women, US, 1999-2001
Site
Risk
All sites
Breast
1 in 3
1 in 7
Lung & bronchus
1 in 18
Colon & rectum
1 in 18
Uterine corpus
1 in 38
Non-Hodgkin lymphoma
1 in 56
Ovary
1 in 68
Melanoma
1 in 78
Pancreas
1 in 81
Urinary bladder
1 in 88
Uterine cervix
1 in 130
Source:DevCan: Probability of Developing or Dying of Cancer Software, Version 5.2 Statistical Research and
Applications Branch, NCI, 2004. http://srab.cancer.gov/devcan
Lifetime Probability of Developing Cancer,
By Site, Men, US, 1999-2001
Site
All sites
Prostate
Risk
1 in 2
1 in 6
Lung and bronchus
1 in 13
Colon and rectum
1 in 17
Urinary bladder
1 in 28
Non-Hodgkin lymphoma
1 in 46
Melanoma
1 in 53
Kidney
1 in 67
Leukemia
1 in 68
Oral Cavity
1 in 73
Stomach
1 in 81
Source: DevCan: Probability of Developing or Dying of Cancer Software, Version 5.2 Statistical Research and
Applications Branch, NCI, 2004. http://srab.cancer.gov/devcan
2005 Estimated US Cancer Deaths*
Men
295,280
Women
275,000
27%
Lung and bronchus
15%
Breast
10%
10%
Colon and rectum
Pancreas
5%
6%
Ovary
Leukemia
4%
6%
Pancreas
Esophagus
4%
4%
Leukemia
Liver and intrahepatic
bile duct
3%
3%
Non-Hodgkin
lymphoma
Non-Hodgkin
Lymphoma
3%
3%
Uterine corpus
2%
Multiple myeloma
Urinary bladder
3%
2%
Brain/ONS
Kidney
3%
All other sites
24%
Lung and bronchus
31%
Prostate
10%
Colon and rectum
ONS=Other nervous system.
Source: American Cancer Society, 2005.
22%
All other sites
Gilda Radner’s Story
Formerly of Sat. Night Live; was married to actor Gene Wilder

Complained to physician of .....
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Died of Ovarian Cancer in 1989
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Fatigue, abdominal pain and bloating
Symptoms progressively got worse
General population: 1 in 70 chance of getting Ovarian Cancer.
Not given ultra-sound or blood tests for Ovarian Cancer.....Why
not?
Did not mention: Aunt & Grandmother died of
ovarian cancer

Makes Gilda’s chances of ovarian cancer: 1 in 2
Cancer Case Study
The cell cycle out of control
An Unavoidable Loss of Control
(Available at the Lecture Note section of the class website)
Questions we’ll try to answer
1.
2.
3.
4.
5.
6.
7.
How do body cells (somatic cells) divide?
What is mitosis and what happens during cell
division?
What controls the timing and location of cell
division?
Why do some cells become cancerous?
What can we do to stop, prevent, and recognize
cancer?
How are gametes (sex cells) produced?
What is meiosis and what happens during the
process?
What is cancer?
Cancer is a genetically dictated loss of cell
cycle control
Cancer cells cannot stop dividing
1.
2.

form a large mass of immortal cells  malignant
tumor
Cell cycle
3.

Activities of a cell from one cell division to the next
Cancerous cells arise in everyone…...
4.

Why doesn’t everyone get cancer?
The Cell Cycle

Things that must happen before a cell divides:
In the nucleus
1. _________________________________________________
Cell organelles
2. _________________________________________________

What must happen to the chromosomes during
cell division?
3. __________________________________________________
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
Daughter
cells
Cell growth +
normal cell
activities
Synthesis of DNA
(chromosomes replicate)
S-phase
Interphase =
G1, S, G2
The Events of Interphase
Interphase—the phase between cell divisions

Divided into 3 phases
S ______________________________________
G2 ______________________________________
G1 ______________________________________

What happens in each phase?
How long does G1 Last?
G1 can vary greatly
a.
Can last indefinitely

b.
e.g. Liver & kidney cells
Can live months to years w/o dividing


e.g. Nerve & muscle cells
Usually never divide (G0)
Cell Division

Cell Division consists of two parts
1. Mitosis
Division of the nucleus to form 2 complete nuclei.
2. Cytokinesis
Division of the cytoplasm to form two cells

What needs to happen to the chromosomes prior
to Mitosis?

During mitosis?
Sketch of a duplicated chromosome
Each Chromatid has
One DNA molecule
1.
2.
How do
sister
chromatids
compare
genetically?
What
happens to
sister
chromatids
during
meiosis?
Kinetochore
Sister chromatids
Centromere
Spindle fibers
The chromosome cycle
Mitosis—sister
chromatids separate
One-chromatid
chromosome
Two-chromatid
chromosome
One-chromatid
chromosome
S-Phase: DNA Replication
Interphase
G1
G1
Human Life Cycle
Mitosis
1.
Produces somatic cells
Daughter cells are
genetically identical
to parent cell


2.
Sperm (23 C)
Fertilization
Fertilization
Zygote (46 C)
Meiosis



Produces gametes
A reductive division
(46 C  23 C)
Daughter cells are
genetically different
Egg (23 C)
Mitosis
Meiosis
Adult Human
(Somatic cells: 46 C)
Meiosis
Normal Karyotype of Human Chromosomes
1.
2.
3.
4.
5.
How do you inherit
chromosomes?
How many pairs of
chromosomes in this
Karyotype?
What are
homologous
chromosomes?
What gender?
Sex vs. autosomal
chromosomes?
Sex chromosomes determine a person’s gender
1. Humans have 46
chromosomes:


Sex chromosomes
2.


3.
44 autosomal
chromosomes
2 sex chromosomes
Female: XX
Male: XY
Diploid number
(2n) vs. haploid
number (n) of
chromosomes?
Two sets of 3
chromosomes
A pair of
homologous
chromosomes
Haploid cell,
n = _______
Diploid cell, 2n = ____
Haploid cell, n = ______
One set of non-homologous
chromosomes
One set of
non-homologous
chromosomes
Mitosis: Division of the Nucleus
View Animation of mitosis
1.

2.
Go to link found at the ALE section of the class website
See the following slides for diagrams of
each step of mitosis
Interphase to Prophase
DNA is replicated in the
nucleus
Chromatin begins
to coil—makes it
more compact
Prophase to Prometaphase
Chromatin continues to
coil, making it more
compact. Chromosomes
are now visible: consist of
identical, paired sister
chromatids.
Nuclear envelope breaks
down. Spindle fibers
(microtubule proteins) attach
to centromeres, resulting in
movement of chromosomes.
Metaphase to Anaphase
Telophase and Cytokinesis
Modeling Mitosis w/ Pipe Cleaners
for a cell with 3 pairs of Chromosomes
3 pairs of chromosomes: 2n = 6
1.
•
•
2.
3.
4.
5.
6.
Diploid Number ??
Haploid Number ??
What does one pipe cleaner represent?
How do you represent a duplicated
chromosome?
What do the colors represent?
What are Homologous chromosome?
What do the different sizes represent?
Modeling the Cell Cycle for a Cell containing
3 pairs of Chromosomes
Go through entire process: S  G2  M  G1
Ask each other these questions as you model mitosis
•
•
1.
2.
3.
4.
5.
How many molecules of DNA does one pipe cleaner represent?”
What do two pipe cleaners twisted together represent?”
What do the chromosomes look like from this organism just before
the S phase?
•
How many chromosomes are present?
What do the chromosomes look like from this organism just after
the S phase?
•
How many chromosomes are present?
What is happen in the cell during each phase of the cell cycle?
Regulation of Cell Division
What evidence in your own life do you have
that cell division is regulated
by your body?
1.


2.
Left ear is about same size as right ear—Why?
A cut your finger heals, but the skin doesn't just keep
growing—Why?
What normally controls cell division?
Contact Inhibition
Cells do not normally grow or divide when in
contact w/ other Cells
1.


E.g. Cultured cells in a petri dish 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 may migrate in culture.
2.

Stop moving when touch other cells due to contact
inhibition of cell movement.
Cancer Cells
No Contact inhibition
1.


continue growing and moving when they touch other cells.
Pile up to form tumors
Metastasize
2.

Cancer cells migrate to other parts of the body—the cancer
spreads
Growth Factors
3.



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
differentiates
Only one daughter
Cell divides
Actively dividing cells
(basal cells):
controlled by
growth factors
Both daughter
cells divide
Growth control in a normal cell
Signaling cell
Growth factor
Growth factor binds to receptor
Receptor sends a signal
to the nucleus
target cell
Nucleus
target cell enters
S-phase and then
divides
Growth Factors: Stimulate Cell Division
Chemical messengers produced in one part of
the body, but effect cells elsewhere
Travel in the blood and other body fluids
Bind to Membrane Receptors, like a key fitting
into a lock.
1.
2.
3.

4.
5.
Stimulates a cell to divide
Each receptor binds to a different growth
factor.
Different cell types are stimulated by different
growth factors.
Several ways to get faulty growth control in a cancer cell
2.
1. Cell might
produce
its own
growth
factor
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
Cancer: It’s all in the Genes
Proto-oncogenes
1.
Normal genes that code for growth factors
Active in actively dividing tissues (e.g. skin)
Sometimes mutate into......
•
•
•
Oncogenes:
2.
genes that cause cancer
produce too much growth factor
•
•


Over stimulate mitosis
Oncogenes are rarely inherited.....Why?
Tumor Suppressor Genes
Tumor Suppressor Genes
1.
•
Code for Proteins that turn off mitosis
e.g. p53 gene
p53 Gene
2.
•
•
3.
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
1.
How many p53 genes did you inherit? Why?
2.
How many p53 genes need to mutate before a
cell becomes cancerous? Why?
BRCA 1
Breast Cancer Susceptibility Gene
1. BRCA 1 is a Tumor Suppresser gene
2. If a women inherits BRCA 1 she has a
a.
b.
c.
d.
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 Role of the
Environment in Causing Cancer
1. Certain Viruses, toxins, or Radiation may lead to
a p53 mutation
2. 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.
Summary of the Characteristics of Cancer Cells
Immortal
Metastasize: Spread into other tissues
Not subject to contact inhibition
Have lost the genetic ability to stop dividing—
mutations to...
1.
2.
3.
4.
•
•
Tumor Suppressor Genes (e.g. p53, BRCA1)
Growth factor Genes
Cancer is heritable: Cancer cells give rise to cancer
cells
Are Dedifferentiated
5.
6.
•
less specialized than the cell it came from)
Therapeutic Strategies:
Attack Actively Dividing Cells
Since cancer is uncontrolled cell division, all
treatments involve the cell cycle.
Phase-specific chemotherapies


Prevent cells from entering S-phase
2. Block the S-phase
3. Block the M-phase (mitosis)
1.
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.

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
1. May affect all rapidly dividing cells
2. Which cells divide rapidly?
a. Hair follicle cells
b. Skin cells
c. Cells lining digestive tract
d. Blood stem cells
• Divide to produce???
So.... What would be the side effects?
Side Effects of Chemotherapy
1. Lose hair
2. Wounds don’t heal well
3. Destroy lining of digestive tract
• nausea and severe bacterial infection
4. 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
1.
•
2.
3.
4.
5.
6.
7.
8.
Fiber speeds passage through digestive tract decrease risk of
colon cancer
Do not smoke
Drink alcohol in moderation or not at all
Exercise regularly
Do not become overweight  fat cells produce estrogen,
a growth factor  increases risk of breast cancer
Limit dietary fat  animal contains growth hormones
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
the body
I - indigestion or difficulty swallowing
O - obvious change in a wart or mole
N - nagging cough or hoarseness
of
Preconceptions Revisited
Evaluate your responses to these questions
1. What is cancer?
2. How are cancerous cells different than normal
cells?
3. How do you get cancer?
i.e. What makes normal cells become cancer cells?
Mitosis and Meiosis Practice Problems
1.
2.
3.
4.
5.
6.
7.
The phase of mitosis in which sister chromatids are separated is called
A. prophase.
B. metaphase.
C. anaphase.
D. telophase.
The phase of mitosis in which chromosomes condense is called
A. prophase.
B. metaphase.
C. anaphase.
D. telophase.
The phase of meiosis in which the nuclear membrane is dismantled is called
A. prophase I.
B. anaphase I.
C. prophase II.
D. metaphase II.
The phase of meiosis in which sister chromatids are separated is called
A. metaphase I.
B. anaphase I.
C. anaphase II.
D. metaphase I
Most of the problems with chromosome numbers in cells are a result of
A. alcohol.
B. U.V. light
C. non-disjunction.
D. mitosis
List four differences between mitosis and meiosis.
Cite two ways that allow for genetic variation in an organism from meiosis.
Mitosis Practice Problems
1.
2.
Identify the stage of mitosis
for cell #1 below.
Identify the stage of mitosis
for cell #2 below.
3.
4.
Identify the stage of mitosis
for cell #3 below.
Identify the stage of mitosis
for cell #4 below.
Mitosis Practice Problems
1. Identify the stage of mitosis for cell #4 below.
2. A diploid cell is one that
a. has two homologues of each chromosome.
b. is designated by the symbol 2n.
c. has chromosomes found in pairs.
d. All of the above
Mitosis and Meiosis Practice Problems
1.
2.
3.
4.
5.
During anaphase of mitosis in humans or other diploid organisms, how many
chromatids does each chromosome have as they move toward the poles?
During anaphase I of meiosis, how many chromatids does each chromosome
have as they move toward the poles?
During anaphase II of meiosis, how many chromatids does each chromosome
have as they move toward the poles?.
A student is simulating meiosis 1 with chromosomes that are red long and
yellow long; red short and yellow short. Why would you not expect to find both
red long and yellow long in one resulting daughter cell?
If there are 13 pairs of homologous chromosomes in a pre-sperm cell, how many
chromosomes are there in a sperm? How many chromatids?
Mitosis and Meiosis Practice Problems
Mitosis and Meiosis Practice Problems
Mitosis and Meiosis Practice Problems
Control of Cell Cycle and Cancer Practice Problems
What role do each of the following play in
controlling the cell cycle and in cancer?

1.
2.
3.
4.
5.
6.
Proto-oncogenes
Oncogenes
Tumor Suppressor genes
Growth factors
p53 gene
BRCA 1 gene