L12- Biochemistry of Cancer

Question 1

What is the difference between carcinomas, sarcomas, leukemias and lymphomas?

Answer 1

Carcinomas arise from epithelial cells. Sarcomas: connective tissues, muscle, cartilage, fat, or bone. Leukemias and lymphomas: blood cells.

Question 2

What are tumor suppressor genes? List some examples of proteins encoded by these genes.

Answer 2

They are genes that encode proteins that help control cell growth and proliferation. Generally, the proteins encoded by tumor suppressor genes exert a repressive effect on the cell cycle. (Well known examples include p53, pRb, WT1, BRCA1, BRCA2, NF1, APC and PTEN.)

Question 3

True or False. Having one functional allele of Rb is protective against cancer.

Answer 3

True. Loss of both alleles is necessary for tumor formation. This is true of most tumor suppressors, although p53 is a notable exception.

Question 4

True or False. The retinoblastoma gene is a proto-oncogene.

Answer 4

False. RB is a tumor suppressor gene.

Question 5

Which cyclins are involved in inactivating pRB?

Answer 5

Cyclins D and E.

Question 6

Which transcription factor is inactive when bound to pRB?

Answer 6

E2F.

Question 7

When pRB is phosphorylated by cyclin-dependent kinases, it releases the molecule E2F. What is the role of E2F in the nucleus?

Answer 7

It stimulates the synthesis of proteins required for the S-phase of the cell cycle such as the polymerase-alpha/primase complex.

Question 8

What condition is caused by germline mutations of the gene that encodes p53?

Answer 8

Li-Fraumeni syndrome.

Question 9

What is the outcome with regards to cell survival when p53 detects DNA damage in the cell?

Answer 9

There are two possible outcomes: p53 may either arrest the cell at the G1/S checkpoint so that DNA can be repaired, or if the damage is too extensive, p53 may induce apoptosis.

Question 10

Which gene is a target of p53 when it comes to halting the cell cycle?

Answer 10

The gene for p21, which codes for a protein that is able to halt the cell cycle in the G1 phase.

Question 11

How does p21 halt the cell cycle?

Answer 11

It binds to and inhibits the cyclin-CDK2 complex. Since CDK2 activity is required for the cell to advance through the G1/S checkpoint, inhibiting cyclin-CDK2 will halt the cell in the G1 phase.

Question 12

True or False. The p53 gene is tumor suppressor gene.

Answer 12

True.

Question 13

What are proto-oncogenes?

Answer 13

They are genes that encode growth-promoting proteins.

Question 14

What are oncogenes?

Answer 14

They are mutated copies of proto-oncogenes.

Question 15

How many alleles of a proto-oncogene must be mutated before tumor formation can occur?

Answer 15

One.

Question 16

What family of receptors binds to PDGF and insulin?

Answer 16

Tyrosine kinase receptors.

Question 17

Where are tyrosine kinase receptors located in the cell?

Answer 17

The cell membrane.

Question 18

What oncogene encodes part of the PDGF receptor?

Answer 18

The sis oncogene.

Question 19

Where are steroid receptors located in the cell?

Answer 19

They can be found in the cytoplasm or nucleus.

Question 20

What family of receptors binds to glucagon?

Answer 20

The seven trans-membrane spanning receptors. This large class of receptors are also known as 7TM receptors and GPCRs (G-protein coupled receptors).

Question 21

What does the erb-B oncogene encode?

Answer 21

It encodes a modified form of the EGF receptor. The result is that the receptor will always produce intracellular signals, even in the absence of EGF.

Question 22

When bound to GTP, RAS is in its ____________ (active/inactive) form.

Answer 22

Active.

Question 23

How does a mutation of the ras gene affect the signaling activity of its protein product, RAS?

Answer 23

Mutations that occur in the GTPase domain of RAS will reduce the protein’s ability to hydrolyze GTP. This will result in excessive signal transduction to the nucleus. 25% of cancers involve Ras mutants.

Question 24

True or False. The neurofibromatosis type 1 (NF1) gene is a tumor suppressor gene.

Answer 24

True. The gene contains a GAP (GTPase activating domain).

Question 25

How does a mutation in the NF1 gene affect the signaling of its protein product, neurofibromin?

Answer 25

NF1 deletion mutations lead to loss neurofibromin GAP domain (GTPase activating domain) activity. As a result, neurofibromin will not be able to activate the GTPase on RAS, so RAS will be “stuck” in its on position, sending excess signals to the nucleus.

Question 26

What is the most common way in which a cell can regulate the activity of its transcription factors?

Answer 26

Reversible phosphorylation.

Question 27

Which transcription factors form a complex on AP1 sites on DNA?

Answer 27

Fos and Jun. The complex of Fos and Jun is known as AP1.

Question 28

How does a mutation in the AP1 gene affect cell growth?

Answer 28

Normally, the expression of Fos and Jun increases only transiently. A mutation that will affect the transient nature of Fos and Jun expression may lead to constitutive expression of these proteins. As a result, cell growth will be continuous instead of transient.

Question 29

Overexpression of which transcription factor is associated with increased risk of developing Burkitt’s lymphoma?

Answer 29

MYC.

Question 30

What is the role of the transcription factor MYC?

Answer 30

It binds to enhancer sequences and recruits histone acetyltransferases, thereby regulating the expression of many genes. It helps to force cells forward through the cell cycle.

Question 31

What is the nature and location of the mutation associated with Burkitt’s lymphoma?

Answer 31

The mutation is a reciprocal translocation between the c-myc gene and the immunoglobin heavy chain genes (IgH).

Question 32

Simian virus 40 (SV40) T-antigen binds which tumor suppressor proteins?

Answer 32

p53 and pRb.

Question 33

The E6 gene of human papillomaviruses binds to which human tumor suppressor gene product?

Answer 33

p53.

Question 34

The E7 gene of human papillomaviruses binds to which human tumor suppressor gene product?

Answer 34

pRB.

Question 35

How do the viral proteins of human papillomaviruses affect human pRB?

Answer 35

The viral E7 protein binds to pRB to induce the release of the E2F transcription factor, allowing E2F to bind promoters and activate the transcription of genes in an unregulated manner.

Question 36

How do the viral proteins of human papillomaviruses affect human p53?

Answer 36

The viral E6 protein is able to bind to human p53 and induce the proteolysis of p53 via the ubiquitin pathway. This allows the cell to not only go through the cell cycle without checking for DNA damage, but also to evade apoptosis.

Question 37

Which viral encoded protein in the human papillomaviruses genome is most important for viral genome replication?

Answer 37

E1.

Question 38

Which viral encoded protein in the human papillomaviruses genome is required for viral genome transcription?

Answer 38

E2.

Question 39

What are the six pathologic characteristics of tumor cells?

Answer 39

1. Self sufficiency through growth signals (for example, activation of RAS) 2. Insensitivity to anti-growth signals (for example, loss of pRB) 3. Evasion of apoptosis 4. Limitless replicative potential (for example, activation of telomerase) 5. Sustained angiogenesis 6. Metastasis.

Question 40

Adenomatous polyposis of the colon is associated with a mutation of which tumor suppressor gene?

Answer 40

APC.

Question 41

What is cancer metastasis?

Answer 41

The spread of cancer from one part of the body to another.