Download Table 3. Consequence of Series of Numbers Rolled

Part 3. When Cells Go Wild – the Uncontrolled Nature of Cancer Cells
Having an understanding of the cell cycle, including mitotic cell division, has been
one of the main foci of cancer treatment research. Why? Scientist are trying to better
understand the mechanisms which tightly regulate the process of cell division in order to
pinpoint faulty machinery that results in the development of uncontrolled cell division,
cancer. Research has shown that there are two types of mutation that can disrupt cell
division and lead to cancer. Proto-oncogenes are genes that code for growth factors which
stimulate or jumpstart the cell cycle. Mutations of proto-oncogenes leave the cell cycle
turned on. Tumor-suppressors genes code for the proteins that inhibit the cell cycle.
Mutations of tumor suppressors turn off genes that allow the slow down of the cell cycle,
DNA repair and cell death.
A mutation in a proto-oncogene creates an oncogene. Oncogenes are cancercausing genes, which overstimulate cell division and allow the cell to override the G1
checkpoint. Many well-known oncogenes lie in the ras gene family. Mutation of the rasK
is found in about 25% of lung cancers, 50% of colon cancers, and 90% of pancreatic
cancers. Another well-known oncogene is HER2 involved in 20% of breast cancer tumors.
In contrast, a mutation in a tumor-suppressor gene results in failure of the
inhibitory proteins to halt cell division. Some tumor-suppressor gene mutations may also
inhibit the ability of proteins to detect and repair DNA damaged during cell division. Cell
division is then encouraged and future mutations go unchecked. The p53 tumor-suppressor
has been implicated in more human cancers than any other gene. Normally, the p53 gene
checks the DNA and when damage is detected, makes the decision whether to fix the
mistake or, when unable to correct it, commit cellular suicide. When p53 is mutated it
allows the cell cycle to continue with DNA unchecked, allowing for the accumulation of
numerous future mutations.
When a cell undergoes combinations of these types of mutations, the cell is allowed
to grow unchecked creating a large mass of cells termed a tumor. When the tumor
remains encapsulated and non-invasive to surrounding organ function it is called a benign
tumor. These tumors are referred to as non-cancerous. If cells within the tumor acquired
tumor-suppressor mutations that inhibit proteins to check DNA, there is the opportunity for
many new mutations to occur. These future mutations increase the virulence of the tumor
allowing it to become invasive, unencapsulated, and, at times, able to spread to distant
locations within the body. At this point the tumor would be called a malignant tumor.
Malignant tumors are cancerous.
Cancer Simulation Game
In the following activity the role of mutation in the development and progression of
cancer will be simulated. During the activity each member of the group will take turns
rolling four dice. Based on the series of numbers rolled, the individual will accumulate
various mutations. Each of these mutations will affect the individual’s final cancer
diagnosis. It is important to realize that this simulation uses single mutations to
demonstrate tumor formation and development of many cancer characteristics. In reality,
changes reflect the interplay of various mutations. Also actual cancer development does
not fit a “typical” sequence. Mutation is a random event unique to the individual.
1
1. Form a group of four or five students. Each member of the group needs to obtain four
dice.
2. Each member of the group is to simultaneously roll their individual set of four dice
once and record the resulting series of numbers within the first column labeled Number
Series Rolled within Table 4. When recording the series of numbers rolled write the
numbers in increasing numerical order. This first series of numbers rolled indicates the
mutations you were born with. Repeat this step until each member has rolled and
recorded the resulting number sequences a total of fifteen times within Table 4.
3. Once all number series have been recorded, use the key found in Table 3 to determine
the consequence, if any, of the particular number series rolled. Then in Table 4 place a
check within the appropriate box.
4. When finished, examined the check marks made in Table 4. Were check marks made
in the last four columns? If the answer is yes, start with the first check mark made in
one of the last four columns. Did accumulating both a proto-oncogene and tumor
suppressor mutation precede this check mark? If no, continue to ask this question for
each of the additional check marks found in the last four columns. If (or when) yes,
place a dark underline under this entire row. Disregard any check marks made in the
last four columns above this line. This line indicates the moment in which a malignant
tumor developed.
5. Fill in the group’s final cancer characteristic information on the Overall Class Cancer
Characteristics overhead. When all groups have filled in their data, record the results
into Table 5. Observe trends in the cancer characteristics of the entire class.
1. Did you have cancer at birth (after round one)?
2. How many people in your group had cancer at birth (after round one)?
3. How many mutations did you have at birth?
4. How many mutations did the other people in your group have at birth?
,
5. Can you have mutations that lead to cancer without getting cancer?
,
,
6. If you are born without inherited mutations, can you develop cancer later in life?
Why?
7. If you are born with mutations that can lead to cancer, can you pass these mutations
to your children? Why or why not?
8. If you accumulate mutations later in life by being exposed to carcinogens, can you
pass these mutations to your children? Why or why not?
______
9. What are four ways your body can cope with mutations in order to prevent them from
leading to cancer?
2
10. How do mutations of proto-oncogenes disrupt the normal cell cycle? Which
checkpoint is involved?
11. How do mutations of tumor suppressor genes disrupt the normal cell cycle? Which
checkpoint(s) are involved?
12. Why can’t you get a malignant tumor until after a proto-oncogene and tumor
suppressor gene have mutated?
______
13. Why can’t anigoenesis, contact inhibition, or metastasis occur until after a protooncogene and tumor suppressor gene have mutated?
14. How would exposing everyone in the class to cigarette smoke over many years
change the total numbers you got in Table 5?
15. What is the average number of rounds it took the people in your group to develop a
malignant tumor?
How old would the average person be when he gets a
malignant tumor if every round represents 5 years of life?
16. How many people in your group could have organ failure from cancer (hint: which
vocabulary word in Table 3 leads to organ failure)?
17. Whose cancer in your group would be considered the worst in terms of staging
(hint: metastasis, invasion of nearby tissues and larger-sized tumors are characteristic of
later-stage cancers. Which columns in Table 4 indicate metastasis, the ability to grow
large tumors and invasion of nearby tissue)?
3
Table 3. Consequence of Series of Numbers Rolled
Numbers Rolled
Consequence
(in any order)
Any combination No mutation has occurred.
of numbers not
found below
A mutation has occurred within a cell’s proto-oncogene. An oncogene
A pair
has resulted allowing over stimulation of the cell’s cell cycle.
Ex. 2251 or
Potentially, this cell may be destroyed by the immune system or a
3324
benign tumor may form.
A mutation has occurred within one of a cell’s tumor-suppressor genes.
A Run of Three
The resulting inhibitory protein no longer suppresses the cell’s division
Ex. 1232 or
and allows its DNA to go unchecked. Potentially, this cell may be
2342
destroyed by the immune system or a benign tumor may form.
A mutation has occurred within a single tumor cell. The cell’s gene
that is responsible for promoting blood vessels formation causes
Three of a kind angiogenesis to occur. During this process the cell secretes substances
that encourage blood vessels to form a close network surrounding the
Ex. 4442 or
developing tumor. The tumor will now develop access to the nutrients
5553
and oxygen needed for significant growth and development. The
development of angiogenesis can lead to the failure of surrounding
organs.
A mutation has occurred within a single tumor cell. The cell’s gene,
Run of 4
that requires a cell to stop dividing when it contacts its neighboring
Ex. 1234, or
cells, has mutated. The result of this mutation is contact inhibition.
The cells can pile on top one another without restraint to form large
2345
tumors.
Two mutations have occurred with cells of the tumor: The first
mutation has occurred within a gene that requires a cell to maintain
contact with an underlayer of cells, anchorage dependence. The
2 Pair
result of this mutation is the ability of the cell to dislodge from the
Ex. 2233 or
original tumor. The second mutation has occurred within a gene that
controls the production of an enzyme called proteinase. The result of
4411
this mutation is the ability of the cell to produce proteinase, which
breaks through tissue enabling the cell to gain access to a blood vessel.
The cell is now able to travel and metastisis occurs.
A mutation has occurred within a single tumor cell gene that controls
the production of telomerase. In a normal cell there are sequences at
Four of a Kind the end of DNA strands called telomeres. After each cell division the
length of these sequences is shortened. After approximately fifty
Ex. 3333 or
divisions the shortened length of the telomeres signals a cell to stop
2222
dividing. The result of this mutation is the ability to produce
telomerase, which maintains the length of telomeres so cells basically
become immortal, able to divide continuously.
4
Table 4. Individual Data Record
Round
Number
Series
Rolled
Types of Mutations
No
Mutation
Protooncogene
Mutation
TumorSuppressor
Mutation
Angiogenesis
Ability
Contact
Inhibition
Ability
Telomerase
Production
Anchorage
Dependence
Mutation/
Proteinase
Production
Metastasis
X
X
X
X
1
First roll indicates the mutations you were born with.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Total
X
X
Did you have at least one check in one of the last four columns after accumulating both a proto-oncogene and tumor suppressor
mutation?
Yes = malignant tumor formation No = benign tumor formation or no effect
Did you have at least one check mark in the last column after accumulating both a proto-oncogene and tumor suppressor mutation?
Yes = metastasized No = did not metastasize
5
Table 5. Overall Class Cancer Characteristics
Group
1
Number of
Individuals Who
Did Not
Experience Cell
Mutation
Number of
Individuals within
the Group Who
Potentially
Developed a
Benign Tumor/
No Effect
Number of
Individuals within
the Group Who
Potentially
Developed a
Malignant Tumor
Number
Individuals within
the Group Whose
Tumor Developed
the Ability to
Metastasize
2
3
4
5
6
TOTAL:
6