4.15 MolecularBio of Cancer Flashcards
Tumor suppressor genes known as
caretaker gene, gatekeeper gene, landscaper gene.
Are cancers genetic?
Some are. Some are sporadic.
Viral induced cancer example?
HPV
Root cause of all Neoplasms?
Damaged DNA
What is p53
Potent tumor suppressor implicated in many tumors.
What induces tumors?
Carcinogens
If there are multiple locus contributing to a phenotype this is known as
Locus heterogeneity
What is the role of proto-oncogenes used for normal cell development?
Regulation of cell cycle
Regulation of differentiation
Regulation of senescence
What is transformation?
The process by which a cell loses its ability to remain constrained in its growth properties
What do tumor suppressor genes do?
They either dampen or repress up-regulation of the cell cycle or promote apoptosis.
- Repress the continuation of the cell cycle
- Link entrance of cell cycle to undamaged DNA
- Link apoptosis to damaged DNA
- Adhesion/contact inhibition upkeep
- DNA Repair proteins
Why is getting frequent sunburns related to cancer?
When you burn, your cells will apoptosis and creates fresh new layer of cells. When there are repeated burns and constant apoptosis it can lead to mutation and cancer
How can you get retinoblastoma?
Inherited- gets one bad copy, then gets a mutation in the other good allele
Sporadic- has two unlucky mutations in both copies
Difference is whether you inherit a bad copy, or get 2 good ones
What gene mutations occurs in Retinoblastoma?
Chromosome 13, RB1 gene
What class of cancer causing gene does retinoblastoma fall? Oncogene or tumor supporessor gene?
Tumor suppressor because it is knocking out something
Explain the two hit hypothesis?
Both alleles for a tumor suppressor must be mutated out as one is haplosufficient for tumor suppression
What suppressor genes do not follow the two- hit rule and why?
P53 does not it is a potent tumor suppressor
I have a proto-oncogene that is regulating the cell cycle. A mutation in that gene creates a growth hormone receptor that is constitutively “on.” This mutation is a
Gain of function mutation
I have a tumor suppressor gene that needs a “two-hit” to take out. The mutation that I am creating if I need to hit both alleles to affect the phenotype is a
Loss of function mutation
If a oncogene can create an oncogenic state by mutating one copy of a proto-oncogene, the oncogene is probably going to be a ____ mutation to the proto-oncogene.
Dominant
A tumor suppressor that needs a “two-hit” would classify the mutated allele as being a ____ mutation.
Recessive
Describe the philadelphia Chromosome
Translocation mutation. BCR and ABL next to each other prevents cells from accidently being activated. This results in leukemia.
What is Senescence?
irreversible state of dormancy
Not always a bad thing, some cells are naturally dormant
Apoptosis
programmed cell death
Not always a bad thing as development requires regulated apoptosis
Can be induced by the immune system
How can DNA repair lead to tumors?
Rate of DNA damage in cells varies between 10,000 to 1,000,000 molecular lesions per cell per day
- Increase chances of mutation
What happens when you have excess Oxygen to the DNA?
ENDOGENOUS DNA DAMAGE: Oxidation of DNA- Reactive oxygen species that creates DNA damage. ROS is created by WBC
Exogenous DNA Damage
Free radicals and ROS can be created by many sources outside of the body
Intercalating agents, viruses and plant toxins
- Aflotoxin- Aspergillus parasiticus and A. flavus
How is DNA repaired when there is a single strand break?
uses complementary strand
How is DNA repaired when there is a double strand
Non-homologous end joining (DNA Ligase IV)
Microhomology-mediated end joining
Homologous recombination (like chiasma formation)
What does DNA use for repair during the G2 phase if needed?
Sister chromatid or homologous chromosome
How is a malignant tumor created?
DNA injury (Dysplasia)–> Continued DNA injury (Carcinoma in situ)–> Further DNA injury (Early invasive carcinoma through basement membrane)–> Invasion of blood vessels lymphatics with metastasis
Cancer grading
Grade I Well differentiated
Grade II- Moderately differentiated
Grade III- Poorly differentiated
What kills you when you have cancer?Why are tumor cells hot?
Cancer cells use up your nutrients. They are hot because they are burning up your sugar and goods.
What is the best cancer therapy?
Assasinate: Immune system boosters. Your cells, immune system fights the cancer
What are other forms of cancer treatment
Cut- surgery
Poison- Chemotherapeutics
Burn- radiotherapeutics
How can we get cancer?
Activation of oncogenes
Destruction of tumor suppressor genes
Describe the cell cycle
b. G1 Growth phase. Most cells in this phase
c. Cycle Check- “Stop signs”
d. S- Duplicate DNA—Form of aneuoploidy. Cell is turned off and no longer reactive. Only concerned of dividing.
e. G2- DNA finished replicating. Rest of cell gets on board.
f. Cycle Check- Checks to see if all cell components are there (Mitochondria, golgi, etc).
g. M- Mitosis metaphase
h. G0- They step out of the cell phase. Will not go through mitosis again. Can’t easily induce them.
How do oncogenes effect the cell cycle
they kill the “stop signs”, cycle checks. This activates the system
What part of the cell cycle do protooncogenes turn on?
G1 phase– same gene involved in gene development
How is the cell cycle regulated?
CDK
