Cancer

Question 1

FDA and supplement regulation

Answer 1

In 2017, the FDA issued warning letters to 14 companies for marketing supplements that can cure cancer but do not have a proven, documentable outcome – 65 products in total

Question 2

Which organism is used to study melanoma?

Answer 2

The zebra fish is a new model organism used to study defective genes
that cause melanoma

Question 3

Ocular melanoma

Answer 3

Affects 6 in every 1,000,000, but 4 friends at Auburn have it- this is an example of a cancer cluster

Question 4

General progression of cancer

Answer 4

1. Initiation- a somatic cell undergoes a mutational event
2. Progression- there is a proliferating stage where the cells experience mutation and genome destabilization and dysregulation of growth control pathways
3. Evasion of cancer cell elimination- precancerous cells
4. Tumor growth and dispersal- angiogenesis and metastasis

Question 5

Precancerous cells

Answer 5

These cells block apoptosis and block killing by cytotoxic T cells through the “don’t kill me” receptor. Therefore, these cells are beginning to avoid elimination by the immune system

Question 6

How do cancer cells versus normal cells grow in culture?

Answer 6

Cancer cells grow in soft agar (semi-solid medium). They will grow, divide, and make clones in this medium. Normal cells are not able to grow in soft agar. Cancer cells also may not require serum depending on the cell, while normal cells always require serum. Cancer cells are able to grow in multiple cell layers (no contact inhibition) while normal cells grow in single layers.

Question 7

Cancer cell proteases

Answer 7

Cancer cells secrete much more proteases than normal cells. Tumors cross the basement membrane and ECM by secreting proteases- this is how they become metastatic

Question 8

How do cancer cells look different than normal cells microscopically?

Answer 8

Cancer cells have atypical karyotypes and abnormal miRNA. Cancer cells are generally smaller, less organized, and have a higher nuclear to cytoplasmic ratio.

Question 9

Physiologically, how do cancer cells behave differently from normal cells?

Answer 9

The telomeres of cancer cells will never shorten. Cell membrane is 10x more permeable than the cell membrane of normal cells, and cancer cells have abnormal RTKs. Cancer cells also secrete their own growth factors (are autocrine).

Question 10

Warburg effect

Answer 10

Cancer cells have figured out how to increase the efficiency of glycolysis so they can make more ATP in an anaerobic environment. Unlike normal cells, they use glycolysis to make energy even in the presence of oxygen.

Question 11

Carcinogenic viruses (4)

Answer 11

1. Rous sarcoma virus identified as carcinogenic in 1911
2. SV40
3. HPV
4. Epstein Barr virus

Question 12

C-SRC

Answer 12

Proto oncogene (normal gene) of rous sarcoma virus

Question 13

SV40

Answer 13

Produces a large T antigen. The virus has to take out tumor suppressor genes to be successful

Question 14

Angiogenesis factors

Answer 14

Some cancer cells (mostly solid tumors) will secrete angiogenesis factors to allow blood vessel formation.

Question 15

HPV

Answer 15

Causes cervical carcinoma and some other types of cancer. Gardasil – first cancer vaccine now for both boys and girls to
prevent up to 90% HPV infections that can cause cervical and other cancers

Question 16

Epstein Barr Virus

Answer 16

Causes translocation of chromosomes and lymphoma

Question 17

Thymine-thymine dimers

Answer 17

This is the most common type of DNA damage due to exposure to UV light. These dimers interfere with both replication and transcription of DNA and stalls the replication fork. Thymine is supposed to bind to adenine, not another thymine, so a normal Watson-Crick base pair can’t form. The process of replication past a lesion in DNA will lead to a segment of DNA in the vicinity of the lesion that is relatively likely to contain mutations caused by errors in replication by translesion polymerase- UV light causes a wide variety of base changes around thymine-thymine dimers.

Question 18

Nucleotide excision repair

Answer 18

Thymine-thymine lesions can be repaired. The lesion is recognized by XP-C proteins and 23B proteins. The complex recruits transcription factor TFIH- its helicase subunits, powered by ATP hydrolysis, partially unwind the double helix. X-PG and RPA proteins stabilize the helix and form a bubble of base. XP-G and other endonucleases cut out the damaged portion so it can be degraded. DNA polymerase repairs the gap in the sequence.

Question 19

How are defective cyclins/CDKs related to cancer?

Answer 19

Once cells commit to each phase of the cell cycle, it’s irreversible. Therefore, cell cycle controllers like CDKs must be carefully regulated. Cyclins are what activate CDKs and they are present only during the phase of the cell cycle that they trigger. Checkpoint controls like p53 work by inhibiting cyclins and CDKs, so if cyclins or CDKs are defective, cancer can result

Question 20

p53

Answer 20

Most human tumors have mutations in either p53 itself or in the proteins that regulate p53. p53 causes an arrest in the cell cycle in response to DNA damage or cause apoptosis

Question 21

Oncogenic p53

Answer 21

The oncogenic form of p53 is a loss of function allele. Cells carrying oncogenic p53 mutations do not arrest to give enough time for DNA damage to be repaired. These mutants have unstable genomes and will accumulate somatic mutations. Also, mutant p53 cells will not enter the apoptotic pathway in response to extensive DNA damage. Therefore, they will continue to proliferate, although a normal cell would have undergone apoptosis

Question 22

Telomerase mutations

Answer 22

An oncogenic mutation that allows uncontrolled cell proliferation. Telomerase is an enzyme responsible for adding telomeres to the end of linear chromosomes. In normal cells, telomeres become shorter every time a cell divides, and only a small amount of telomerase is produced. With controlled cell division, the telomeres should drastically shorten and the cell cycle should arrest, with the cell eventually undergoing apoptosis. Tumor cells prevent this from happening by upregulating telomerase expression to create a state of reproductive immortality

Question 23

Cancer stem cells

Answer 23

In some types of tumors, only certain tumor cells (cancer stem cells) are capable of seeding a new tumor. In these tumors, some cells will cease dividing, but others can continue replicative growth. Stem cells likely give rise to both cells with limited reproductive potential and cells with high replicative abilities. Cancer stem cells have properties similar to normal stem cells, and their behavior is influenced by the tumor microenvironment

Question 24

HDAC inhibitors

Answer 24

Histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Used to treat CML

Question 25

Imatinib

Answer 25

BCR-Abl Protein Kinase causes a “Philadelphia chromosome”. Fusion gene is translated in BCR fusion protein- when phosphorylated, the cell divides and becomes cancerous. The drug slides into the fusion gene and prevents it from being translated. Used to treat CML

Question 26

Chromosomal translocation

Answer 26

In cancer cells, many chromosomes are composites of pieces of different chromosomes. This results from translocation events and occurs in Burkitt’s lymphoma

Question 27

DNA amplification

Answer 27

Select genes, like the genes that code for growth factors, can be amplified and lead to cancer

Question 28

Transcription factors

Answer 28

Induce synthesis of important growth and proliferation proteins. Many oncogenes encode transcription factors.

Question 29

FOS and MYC

Answer 29

2 transcription factors with a clear role in tumorigenesis. They stimulate transcription of genes encoding proteins that promote progression through the G1 phase of the cycle and the G1 to S transition

Question 30

Robert Weinberg

Answer 30

Conducted a classic experiment on oncogenes.
DNA from a human tumor was isolated and put into a 3T3 cell, which causes cancer. Discovered the first tumor suppressor gene- retinoblastoma. Also discovered Ras oncogenes

Question 31

Why is cancer age dependent?

Answer 31

Most cancers increase with age. This suggests that you accumulate more mutations over time. Experiment- MYC and RAS

Question 32

Multi-hit model of cancer

Answer 32

A typical tumor will accumulate thousands of mutations, but only 5 have been selected for because they are drivers of tumorigenesis. The incidence of many types of cancer increases rapidly with age, indicating that it takes decades for multiple mutations to occur. The model has been replicated in transgenic mice. One example is colon cancer, which is slow growing- many people have polyps (precancerous lesions)

Question 33

Do tumors originate from one cell or multiple cells?

Answer 33

One cell- data from women prove it due to X chromosome inactivation