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Flashcards in Cancer Deck (22):
1

What are tumor suppressor genes?

Tumor-suppressor gene tells cells to stop dividing. Mutations cause inactivation of these genes, allowing excessive cell division to occur.

2

What are caretaker genes?

Caretaker genes fix mistakes and protect the genome. When inactivated, mutations in the genome accumulate.

3

What are carcinogens?

Carcinogens are environmental substances that cause cancer
​Tobacco, UV radiation, Alcohol, Lead, Nickel, Asbestos.

4

What are viruses that cause cancer?

HPV spread through physical conduct with infected areas; 90% of people’s immune system will get rid of virus; if not you get cervical cancer. Gardasil will not protect if you already have HPV. Can be detected by regular pap smears; sexually transmitted DNA virus. HPV produces viral protein, E5, which binds to PDGF (growth) receptor and tells cells in the cervix to divide (increases likelihood of getting cervical cancer). Inhibits tumor-suppressor genes, therefore, keeps dividing.
​Hepatitis B and Hepatitis C cause liver infections that develop into liver cancer. ​​Spread through unprotected sex and exchange of blood.

5

What are mutations?

Mutations mostly occur in somatic (body) cells so they are not transferred to offspring. Takes a while for these mistakes to buildup which is why cancer is seen later in life. Ovarian Cancer is almost entirely preventable; ovulation causes cells to divide every month.

6

What are proto-oncogenes?

Proto-oncogenes are normal and healthy, functions to promote cell divisions for wound healing and development. Proto-oncogenes are changed into oncogenes by mutation that make them excessively active (leads to cancer)

7

What is oncogenesis?

Oncogenesis is the cancer forming process. Results of an interplay between genetics and the environment. Most cancers are a result of genes being mutated by carcinogens, or by errors in the copying and repairing of DNA.

8

What is a tumor?

A Tumor is a rapidly proliferating cell type that escaped normal growth restraints and stimulates the growth of vasculature to obtain oxygen. Cells that proliferate quickly, and are in abundant supply, are the most dangerous. (i.e. skin cells, ovarian cells)

9

What is matastasis?

Metastasis is the case in which cells from the primary tumor migrate to new sites where they can form secondary tumors. Complex process, and invasion of new tissues is non-random, depending on the nature of both the metastasizing cell and the invaded tissue. Most cancer deaths are due to invasive, fast growing metastasized tumors. Tissues under attack are more vulnerable if they secrete growth factors and readily grow new blood vessels. Tumor cells are oxygen-starved, and require a blood supply to grow.

10

What makes tissues more resistant to metastasis?

Tissues are more resistant if they produce
1. Anti- proliferative factors which block cell division
2.Inhibitor of proteolytic enzymes that block cancer cell protease used to penetrate tissue.
3.Anti-angiogenesis factors which stop tumor cells from initiating the growth of blood vessels.

11

What are the properties of the transformed cancer cell?

Properties of the Transformed (Cancer) cell include;
Changes in cell morphology
Changes in membrane properties such as;
1. Cell to sell interaction change
2. Cancer cells acquire the ability to grow unattached to the basal lamina (Normal cells have to have something to stick to, to grow, cancer cells do not)
3. Growth control changes (Transformed cells have a reduced requirement for growth fctors (ligands) aka mitogens.)
4. Secretion of plasminogen: activator breaks down lamina.
5. Cytoskeleton changes: relates back to #1 (Loss of actin fibers)
6. Staining patterns are different due to hyper-active biosynthesis (Example: Nucleoli are enlarged, stained darker)

12

Describe cultured tumor cells?

Specefic mutation occur that transform cultured cells into tumor cells. Discovered in an experiment using a cell line of mouse fibroblast called 373 cells. Only grow when attached to the plastic surface of a culture dish, and grow at a low density. They stop growing when they touch other cells, results in a well-ordered mono-layer of 3T3 cells.

13

Describe the classic exeriment?

Genomic DNA from a human bladder carcinoma is added to the 3T3 cells. 1/ 1 million 3T3 cells will take up the mutation and become “transformed”. This cell loses its contact inhibition, and grows into a “focus” (colony). Focus cells now show many of the same characteristics of the original human cancer cells.

14

What is oncogene isolation?

The goal of Oncogene Isolation was to clone the gene responsible for the transformation of normal cells. Took advantage of fact that humans have nearby repetitive DNA sequences (Alu elements). All genomic DNA extracted from the focus is then introduced into a series of viral vectors, all containing fluorescent probes for human Alu elements. Whichever viral vectors showed fluorescence contained human Alu elements, i.e.: the DNA sequence responsible for transforming the 3T3 cells, i.e. the oncogene.

15

What is RasD isolation?

The cloned segment contained a mutated version of the Ras gene, and was termed RasD. Glycine normally found in position 12 was replaced with a valine. Normal Ras protein functions in signal transduction pathways activated by growth factors. Ras has GTPase activity. Toggles between GTP-bound “ON” state, and GDP-bound “OFF” state.

16

What is the RasD oncogene?

RasD breaks down GTP very slowly, so it remains in the “ON” position too long, sending a growth-promoting signal even in the absence of the growth factors normally needed to activate.

17

What is the difference between the proto-oncogene and the oncogene?

Oncogene is any gene that encodes a protein capable of transforming normal cells into cancer cells. i.e.: RasD. Proto-oncogene is a normal cellular gene, that, upon mutation, can become an oncogene. i.e.: Ras. Oncogenes carried by viruses are often derived from proto-oncogenes that were hijacked from the host genome and altered to become oncogenes. If a proto-oncogene becomes damaged it can lead to cancer.

18

What are the problems associated with using cell culture vs. human tissues?

The problem with using cell culture vs. human tissues is that the results suggest that one mutant gene (RasD) transformed the cultured 3T3 cells in a previous slide. In human tissues, loss of only Ras is not sufficient for cancer. It turns out, the 3T3 cells used in the classic experiment were defective in p19ARF, and p53-regulators of cell cycle. If you transfect perfectly normal 3T3’s with RasD mutation,no transformation. Ras mutations are found in many human cancers: Most human colon cancers, bladder cancers, etc, But these cancer cells have other mutations as well. Cancer: a multi-hit phenomenon, more than one mutation.

19

What are proliferating cells?

In order for most mutations in oncogenes to cause cancer, they must occur in dividing cells, so that the mutation is passed on. Mutations in non-dividing cells (most neurons and muscle cells) usually aren’t cancerous.
Brain and muscle cancer are rare conditions in adults. Glial cells are the brain cells that become cancerous.

20

What are the most frequent cancer locations?

Cancer frequently originates at sites of injury or infection. Immune cells migrate to sites of tissue damage, and release growth factors to promote healing. The extracellular matrix is reconstructed during this time, allowing metastasis. These properties may contribute to the establishment and growth of a tumor.

21

What is angiogenesis?

Angiogenesis is the recruitment of new blood vessels that is required for the growth of all tumors. Without blood, the average tumor mass can grow to be only ~ 2 mm in diameter. Because as new cells are dividing on the outside of the tumor mass, older tumor cells are dying within the tumor mass due to lack of nutrients.
o The irregular edges in cancerour mole means that its not enclosed and it's free to move. Can be stimulated by growth factors released from tumor cells. (Basic fibroblast growth factor (bFGF), Transforming growth factor α (TGFα), Vascular endothelial growth factor (VEGF)). Some tumor cells induce surrounding normal cells to synthesize and secrete these growth factors.

22

What predicions does the multi-hit model of cancer say?

1) ALL cells in a given tumor should contain at least some genetic alterations in common, since they all derived from a single progenitor. The analysis of cells from human tumors supports this. (In women, during development, one X chromosome is inactivated. So, the adult female is a genetic mosaic. Yet, cells from a woman’s tumor all have the same inactive X chromosome.)
2) Cancer incidence should increase with age since it takes decades for the required multiple mutations to occur. Assuming mutation rate is constant, incidence of most cancers would be independent of age if only one mutation were required to transform a normal cell into a cancer cell. **Estimated 5-6 mutations are thought to be needed for most cancers to occur.