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 (X-rays) 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 proto-oncogene 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 tumor-suppressor 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=RZhL7LDPk8w
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 tumor-suppressor?
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 tumor-suppressor.
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