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Chapter 25: Cancer

Terms in this set (24)

What is the Warburg effect?
It is an altered energy metabolism where glycolysis happens instead of oxidated phosphorylation, even in the presence of oxygen.

Cancer makes a lot of lactate and less ATP/glucose.
What can cancer mutations be in?
Receptor proteins, DNA repair proteins, intracellular signal transduction proteins (example would be Ras), cell cycle control proteins, apoptotic proteins, transcription factors, and rarely signaling molecules.

More info: within each category, both oncogenes and tumor suppressor genes can be found.
What are two types of tumors? Explain what they are and give examples.
Benign: remains localized and is a problem only if they grow too large, normal tissue function is impaired, or if they secrete toxins or hormones. Example: Wart.

Malignant (Cancerous): invasive. Most cells acquire metastatic features that overcome physical boundaries of tissues like the basal lamina. Example: melanoma.
What is metastasis?
The spread of tumor cells and the establishment of secondary tumors.
Can oncogenic drivers be gain-of-function, loss-of-function, either-or or both?
Either-or.

For loss-of-function, it is the tumor suppressor gene. For gain-of-function, it's the oncogenes.
How is proto-oncogenes implicated when cancer arrives?
Normally gain-of-function, and the mutations are genetically dominant.
How is tumor-suppressor genes implicated when cancer arrives?
Normally loss-of-function, and the mutations are genetically recessive.
How is genome maintenance genes implicated when cancer arrives?

Hint: this is a special class of tumor-suppressor genes.
Normally loss-of-function, and mutations are genetically recessive.
What are the six properties of metaswized tumors?
Sustain proliferative signaling, enable replicative immortality, resist cell death, evade growth suppressors, induce angiogenesis, activate invasion and metastasis.
Explain the general framework for the evolution of cancer. Name the steps, then go into detail on what happens for each step.
1) Initiation, 2) Cancer progression, 3) Evasion of cancer cell elimination, 4) Tumor growth and dispersal.

First, you get a somatic cell that gets a mutation. Genome destabilization happens, along with the loss of regulation of the growth factors in the cell. That cell divides and you get a population of cells with that mutation, then get another mutation. Those cells divide, so now you have a population of cells with more than one mutation. Apoptosis is blocked at this point and block killing by T cells. Then, the cell grows blood vessels through angiogenesis to provide oxygen and nutrients, and take away wastes and carbon dioxide. Finally, metastasis happens and the cells break free of the local environment and spread to a new location in the body to repeat the process.
Since the genetic makeup of most cancer cells is dramatically altered, it causes a lot of problems within the cell. What are some of these problems?

Bonus: Give the domino effect that gene alteration causes. (Steps)
Extra chromosomes, translocations, local amplifications and deletions, various other chromosomal defects.

Bonus: Alters gene ratio -> causes protein ratio imbalance -> stress response for protein folding and and degradation (potential therapeutic targets)
What are the three common oncogenic mutations?
Ras activation, p53 inactivation, telomerase activation.

Ras activation: RPK Ras MapKinase pathway.
p53 inactivation: transcription factor that plays a role in cell cycle arrest, DNA repair, and apoptosis
Telomerase activation: so you can activate forever without losing the chromosome
If you don't maintain your telomeres, what happens?
Without telomeres, breakage-fusion-bridge cycle happens.
What statement about cancer is false?

1) Cancer is caused by the accumulation of multiple mutations in on cell.
2) Cancer often originates in fully differentiated cells.
3) Proto-oncogenes normally promote cell proliferation or survival
4) Tumor-suppressor genes normally inhibit cell proliferation or survival
5) Cancerous cells usually have altered energy metabolism, known as the Warburg effect.
Cancer often originates in fully differentiated cells.
Which of the following is not a fundamental cell property that is altered in cancer?

1) Ability to evade apoptosis
2) Ability to promote growth of new blood vessels
3) Self-sufficiency for growth signals
4) Ability to differentiate into any cell type
5) Ability to go through limitless cell cycles
Ability to differentiate into any cell type.
Which protein is a cell cycle control protein that is encoded by a photo-oncogene?

1) Bax
2) Myc
3) Cyclin D1
4) Ras
5) Rb
Cyclin D1

It is a cell cycle control protein and it's encoded by a photo-oncogene. If you have too much cyclin D1, it will promote entry into the cell cycle.
Which protein is a cell cycle control protein that is encoded by a tumor-suppressor gene?

1) Bax
2) Myc
3) Cyclin D1
4) Ras
5) Rb
Rb

It is a cell cycle protein that is encoded by a tumor-suppressor gene. It controls entry into the cell cycle by getting past START. It is a tumor suppressor gene because if you have one function Rb gene, it can inhibit entry into the cell cycle. It can inhibit going past the restriction point.
Which statement about p53 is false?

1) p53 is phosphorylated by C-CDK hetordimers
2) p53 is mutated in over 50% of human cancers
3) p53 causes cell cycle arrest in response to DNA damage
4) p53 is a transcription factor that relegates genes like CDK inhibitors
5) p53 is usually rapidly degraded after being poly-ubiquitinated by MDM2
p53 is phosphorylated by C-CDK heterodimers.
What is Ras in colon cancer?
It is the second mutation and is a proto-oncogene.
What is p53 in colon cancer?
It is the third mutation and is a tumor suppressor.
What is APC in colon cancer?
It is the first gene mutated and is a tumor suppressor gene. It blocks Wnt from activating Myc. It is also recessive, so it needs both copies mutated. (LOH--Loss of heterozygosity)
What is a multi-hit phenomenon?
It is when different mutations can be involved. Different combinations of mutations may result in the same phenotype.
What do tumor cells make neighboring cells secrete or secrete themselves?

Hint: These are necessary for the growth of blood vessels into the tumor.
Basic fibroblast growth factor (Beta-FGF), transforming growth factor alpha (TGF-alpha), vascular endothelial growth factor (VEGF)
What block new blood vessel growth from tumors?
Angiostatin, endostatin, and antagonists of the VEGF receptor.
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