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The Loss of the Cell Cycle Control

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Part 3: Page S90 Lab Manual
Loss of Cell Cycle Control in Cancer
Prelab Questions for Part 3
• How are normal cells and cancer cells different from each
other?
• What are the main causes of cancer?
• What goes wrong during the cell cycle in cancer cells?
• What makes some genes responsible for an increased risk
of certain cancers?
 What are the roles of tumor-suppressors genes and oncogenes?
 What seems to be genetically wrong in families with a
history of cancer?
Stating a Hypothesis
Do you think that
the
chromosomes
might be
different
between
normal and
cancer cells?
Tumor-suppressor Genes:
 One of the most important molecules relating to
cancer is called p53. It has been called the guardian
of the genome.
 Tumor suppressor genes are normal genes that slow
down cell division, repair DNA mistakes, or tell cells
when to die (a process known as apoptosis or
programmed cell death). When tumor suppressor
genes don't work properly, cells can grow out of
control, which can lead to cancer.
1) Why is p53 important in controlling the cell cycle?
An important difference between
oncogenes and tumor suppressor
genes is that oncogenes result
from the activation (turning on) of
proto-oncogenes, but tumor
suppressor genes cause cancer
when they are inactivated (turned
off).
Inherited mutations of tumor
suppressor genes
 Inherited abnormalities of tumor suppressor genes
have been found in some family cancer syndromes.
They cause certain types of cancer to run in
families. For example, a defective APC gene
causes familial adenomatous polyposis (FAP), a
condition in which people develop hundreds or
even thousands of colon polyps. Often, at least one
of the polyps becomes cancer, leading to colon
cancer.
Acquired mutations of tumor suppressor genes
 Abnormalities of the p53 protein have been found in more
than half of human cancers. Acquired mutations of this
gene appear in a wide range of cancers, including lung,
colorectal, and breast cancer.
 The p53 protein is involved in the pathway to apoptosis.
This pathway is turned on when a cell has DNA damage
that can't be repaired. If the gene for p53 is not working
properly, cells with damaged DNA continue to grow and
divide. Over time this can lead to cancer.
 Acquired changes in many other tumor suppressor
genes also contribute to the development of sporadic
(not inherited) cancers.
Many of the genetic alterations found
in cancer cells are microscopically
visible when chromosomes condense
during mitosis, and can thus be
registered as numerical or structural
cytogenetic abnormalities that can
be studied – including karyotypes.
Chronic myelogenous leukemia, showing the typical 9;22
translocation
Chronic myelogenous leukemia, showing the typical 9;22
translocation
The Philadelphia
chromosome (Ph) is
produced by a
translocation between the
long arms of chromosomes
9 and 22.
Non-small-cell carcinoma of the lung, showing
abnormalities of both number and structure.
HeLa Karyotype
Burkitt’s Lymphoma
Translocation:
misplacement of
chromosome 8
Dermatofibrosarcoma: Chromosomes
Dermatofibrosarcoma
Two distinct cytogenetic features, supernumerary rings
and translocations
You have received a set of chromosomes to build your own
karyotype. Follow all the instructions given on the handout!
For each of the following cases, look at pictures of the chromosomes
(karyotype) from normal human cells. Compare them to pictures of
the chromosomes from cancer cells. For each case, count the number
of chromosomes in each type of cell, and discuss their appearance.
Then answer the following questions.
• Do your observations support your hypothesis?
• If not, what type of information might you need to know in
order to understand your observations?
• If yes, what type of information can you find that would validate
your conclusions?
Abnormal Karyotypes 
Case 1: HeLa cells
Case 2: Philadelphia Chromosomes
For each of the following cases, look at pictures of
the chromosomes (karyotype) from normal human
cells. Compare them to pictures of the chromosomes
from cancer cells. For each case, count the number of
chromosomes in each type of cell, and discuss their
appearance. Then answer the questions in your lab
textbook for this section.
Karyotypes of Cancerous Cells
 Anaplastic large-cell lymphoma # 6
 Burkitt’s lymphoma # 7
 Chronic myelogenous leukemia # 2
 Dermatofibrosarcoma protuberans # 10
 Ewing’s sarcoma # 11
 Follicular lymphoma # 8
 Hela # 5
 Mantle cell lymphoma # 4
 Synovial sarcoma # 9
Analysis of your cancer research
1) Which tissues are affected?
2) Symptoms
3) Treatments
4) Prognosis: forecasting of the probable
course and outcome of a disease,
especially of the chances of recovery
(curable, treatable, terminal for how
long).
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