Molecular Biology of Cancer
• What are the environmental influences that are
cancer-causing?
• What is the difference between an oncogene and
a proto-oncogene?
• What genetic changes convert proto-oncogenes
to oncogenes?
• Reference page 272 (Fig 15.12) to understand
alterations of chromosome structure: relate this
to the statement “Malignant cells are frequently
found to contain chromosomes that have broken
and rejoined incorrectly, translocating
fragments.”
Molecular Biology of Cancer
(responses)
• Chemical carcinogens, physical mutagens (Xrays) or certain viruses
• Proto-oncogene: normal cellular genes-code
for proteins that stimulate normal cell growth
and division
• Oncogene: cancer-causing gene
• “An oncogene arises from a genetic change
that leads to an increase in either the amount
of proto-oncogene’s protein product or
intrinsic activity of each protein molecule”
Cancer Understood
• Explain how the location of the protooncogene being located adjacent to an active
promoter leads to an oncogene.
• What is amplication?
• Explain how a point mutation can change the
gene’s protein product and therefore lead to
an oncogene.
Alterations of Chromosome Structure
3 Main Categories of
Oncogene Conversion
• Movement of DNA within the genome
– Translocation or transposition
– **new controls / new promoter
• Amplication of proto-oncogene
– Increases number of copies of the gene in the cell
• Point mutation in proto-oncogene
– More active or resistance to degradation than
normal protein
• **All growth stimulating**
Proto-oncogenes into Oncogenes
Oncogenes
• http://www.teachersdomain.org/asset/tdc02_
vid_oncogene/
Tumor-suppressors
• Define and explain tumor-suppressor genes in
relationship to cancer.
• What are the functions of normal tumorsuppressor genes?
Tumor Suppressor Genes
• Tumor suppressor genes—proteins prevent
uncontrolled cell growth
• Functions:
– Repair damaged DNA
– Control adhesion of cells to each other
– Cell signaling—inhibit cell cycles
• If altered, the suppression is decreased and
therefore cancer can be the outcome
Ras (30%) versus p53 (50%)
• In general, what is the difference between a oncogene
and a tumor suppressor gene? Relate them to cancer.
• Signal transduction Pathways: A set of chemical
reactions in a cell that occurs when a molecule, such as
a hormone, attaches to a receptor on cell membrane.
The pathway is actually a cascade of biochemical
reactions inside the cell that eventually reach the
target molecule or reaction. Thus, the pathway is a
method by which molecules inside the cell can be
altered by molecules on the outside.
Ras
• Normal ras job:
• What does ras need to do its job?
• How is the oncogene of Ras hyperactive?
p53
• What are the main functions of a normal
functioning p53? (hint: at least 3 ways)
Cancer and Age
• Why does the incidence of cancer increase
with age?
• How does this help explain the predispositions
to cancer that run in some families?
• Explain “dominant oncogenes and recessive
tumor-suppressors”.
• How do active telomerases relate to cancer?
Viruses
• How do they contribute to cancer
development?
• Define retrovirus (use back of book)
BRCA1 and BRCA2
• What does BRCA stand for?
• What type of cancers are these genes related
to?
• What type of genes are these? (oncogenes or
tumor-suppressors)
Metastasis
•
•
•
•
Tumor
Benign
Malignant
Metastasis
Khan
• http://www.youtube.com/watch?v=RZhL7LDP
k8w
Question:
• True or False: A proto-oncogene only makes a
protein when a promoter tells it to.
Answer:
• True
Question:
• True or False: One possible effect of an
oncogene is the inability to repair a damaged
cell.
Answer:
• False
Question:
• What is translocation?
Answer:
• Exchange of information from one
chromosome to another.
Question:
• What does translocation have to do with
promoters and cancer?
Answer:
• The “switched gene” goes to a new location
with a new promoter that tells it to turn on
(make a protein) when it normally would not.
Question:
• What are the three normal jobs of a tumorsuppressor?
Answer:
• Repair damaged DNA
• Control adhesion of cells to each other
• Cell signaling—inhibit cell cycles
Question:
• Was the video showing how a mutated Ras
works or how a mutated p53 works? Explain.
Answer:
• Ras. It was stimulating cell growth, not
stopping it. Ras is an oncogene, not a tumorsuppressor.
Question:
• Why is p53 known as the Guardian Angel of
the Genome? Why is p53 a part of 50% of all
cancers?
Answer:
• It makes sure all the erred cells do not
multiply or continue on with mutations by
repairing, signaling to stop cell cycle, or
signaling apoptosis.
• An error in p53 is very detrimental to cells and
leads to cell overgrowth…aka cancer.
Question:
• True or False: A virus can stimulate cancer.
Answer:
• True
Question:
• True or False: It only takes a single mutation to
cause cancer.
Answer:
• False. This is why the incidence of cancer
increases with age.
Question:
• BRCA genes are ___________________ genes.
Answer:
• Tumor-suppressor