BIOL 207
Biology of Cancer
Fall 2007
Lecture 3: Cell cycle and cell death
Reading: Chap. 2 pp. 18-28
Outline:
1. Cell cycle and cancer
2. Cancer cells have cell cycle defects
3. Apoptosis
4. DNA damage/repair
Lecture:
1. Cell cycle and cancer
 cancer cells are less dependent on external growth factors than are normal cells.
examples of growth factors:
o PDGF=platelet derived growth factor
o EGF=epidermal growth factor
 Growth factors trigger a series of events ultimately stimulating cell growth and
division.
Fig. 2-6 Growth factor signaling of normal cells vs. cancer cells

Cancer calls may have mutant receptor that triggers pathway in the absence of
growth factor.
Cell cycle: Schedule of what goes on in a cell before, during and after cell division.
Fig. 2-7 right panel
M=mitosis, when cells divide
G1=gap1, when cells grow, check nutrient levels
G0=resting stage=quiescence
Cells can exist here indefinitely until they receive a signal to reenter the cell cycle again.
Growth factors often carry such signals.
S=synthesis, DNA synthesis occurs
G2=gap2, cells grow and check to see if ready to divide
2. Cancer cells often display defects in regulating the cell cycle.
a. Growth factors and growth factor receptors can be altered (many are encoded by
cellular oncogenes, for example PDGF=sis oncogene. Result: instead of staying in G0,
cancer cells reenter the cell cycle and go on to divide.
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b. Moving through the cell cycle involves several proteins called cyclins that are
unstable and controlled by regulatory enzymes called cyclin-dependent kinases (cdks)—
kinases add phosphates to other enzymes. Some cancers are associated with mutant
cyclins or mutant cdks.
c. Many cancers have mutations in their tumor suppressor genes, such as the key
regulatory gene, Rb (retinoblastoma, named for the eye cancer most associated with its
loss). Rb interacts with cyclin-cdks to regulate the G1/S restriction point.
Others have mutations in the tumor suppressor p53, which moniters cells for DNA
damage and functions in several cell cycle checkpoints to prevent damaged cells from
dividing.
3. Apoptosis=preprogrammed cell death pathway
Cancers can result from uncontrolled growth. They can also result from not enough
cell death. Fig. 2-13
Cell death is triggered by insults to cells such as too much DNA damage (pathway 2).
o p53 sends a signal to the mitochondrion
o mitochondria release the respiratory chain enzyme cytochrome c.
o cytochrome c triggers a death pathway called the caspase cascade that results in
cell death.
The caspase cascade can also be directly triggered from the outside (pathway 1). Cells of
the immune system secrete molecules that can trigger cells to die. Many abnormal cells
and cancer cells are killed in this way.
In cancers, certain aspects of this pathway can be altered

Bcl-2 is a protein that normally prevents cell death; if overproduced, not enough
cell death occurs, and leukemias and lymphomas can result.

Many cancer-causing viruses produce proteins that interfere with the cell death
pathway.
4. DNA damage, DNA repair and cancer.
Commonly, we find DNA damage causes mutations that lead to cancer. What causes
DNA damage?
 Chemical carcinogens
 Radiation
Fig. 2-15
Some types of environmentally induced DNA damage are
o Depurination (remove G base)
o Deamination (remove NH3 groups from C  makes it a U)
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o Thymine dimers (two adjacent Ts get linked together)
When DNA is replicated, mistakes may be kept, causing mutations.
Cancer results from several mutations in oncogenes and tumor suppressor genes.
Most mistakes in DNA are corrected.
o Fig. 2-16: an example of excision repair. Hereditary skin cancer (Xeroderma
pigmentosum) is associated with mutations in some of the genes for enzymes in
excision repair.
o Mutations in another repair pathway called mismatch repair are associated with
several forms of hereditary colon cancer (HNPCC).
Cancer cells are often genetically unstable and may have severe chromosomal defects.
Fig. 2-19: Philadelphia chromosome associated with chronic myeloid leukemia. The
Philadelphia chromosome is associated with a translocation (Exchange between two
different human chromosomes, 9 and 22.
Note for exam I: need not know in detail Figs. 2-9, 2-12, 2-16,2-17, 2-18.
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