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