Exam 4 L4: Cribbs Cancer I Flashcards
Cancer is ________
Cancer is basic cellular functions “gone wrong” :
Cell proliferation/cell cycle
Cell adhesion
Cell communication
DNA repair mechanisms
Apoptosis
Two conditions required for cancer are:
Two conditions required for cancer:
Uncontrolled cell divion —> tumor
(not all tumors are cancerous, if a tumor is confined its benign)
Tumors spread beyond tissues —-> malignant
Give the names for the following types of cancer:
Benign and malignant epithelial cancer
Benign and malignant muscle/cartilage cancer
Epithelial : Adenoma (benign)….. Carcinoma (malignant)
Muscle/Cartilage: Chondroma (benign)….. sarcoma (malignant)
What is the most prevalent type of cancer?
Carcinoma (malignant epithelial tumors)
Why are carcinoma’s the most prevalent type of cancer?
Epithelial cells undergo many cell divisions and are easily exposed to enviornmental factors in the enviornment
Cells become cancerous from ___________ or _______
Cell becomes cancerous from single genetic mutation or heritable epigenetic event (in order to pass it on to its progeny tumor cells)
Cancer arises from a combo of ___ and ___ changes
Cancer arises from a combination of GENETIC and EPIGENETIC changes
Genetic: Alteration of DNA sequence (low frequency, original event followed by sucessive events in same cell lineage)
Epigenetic: changes in pattern of gene expression without change in gene sequence (methylation, histone modification, etc)
Explain tumor progression
Tumor progression:
One cell gets mutated
Then there is cell proliferation of that mutated cell
Successive mutations create an invasive tumor—> Genetic Instability
Carcinogenesis is related to ______
CARCINOGENESIS is related to MUTAGENESIS
Tumor progression also involves impaired proliferation/apoptosis balance
Explain the two scenarios
Increased cell division with normal apoptosis will create a tumor
Normal cell division with decreased apoptosis will create a tumor
Explain how all of the checkpoints within the cell cycle can play a role in cancer
Also explain telomerase’s role in cancer
Cell cycle has multiple potential sites for abnormalities that lead to uncontrolled proliferation
Some cancers can also be caused to screwed up telomerase
Explain cancer stem cells:
Most cells in a tumor are called ______
Cancer stem cells have the ability to____
Most cells in a tumor are “transit amplifying cells”
Stem cells are self-renewing
Very few cells within a tumor are stem cells. The stems cells are the only ones that have the ability to make new tumors. THis is why radiation and chemo sometimes don’t always work, if they don’t kill stem cells. This is also why if you put a bunch of cancer in a petri dish, only some of them will make new tumors, because only a tiny fraction of the cells were stem cells and even have the ability to make new tumors
How can scientists see tumor cells?
Look at places with high glucose uptake (rapidly dividing cells)
Metastatic Process:
Cell grows as benign in epithelium, cells then become invasive and enter capillary…. (what happens next)
Cells can then travel through the blood stream (fewer than 1 in 1000 will survive to form metastases)
The ones that create new tumors have to be stem cells, and they have to find a good microenviornment
Colonization:
Only a ______ of tumor cells that reach a foreign enviornment are able to survive
Cancer cells that do survive carry mutations and thus are less dependent on intercellular signaling for cell division and survival, and they may also _____
As the tumor enlarges, _______ mechanisms set in
Only a small proportion of tumor cells that reach a foreign enviornment are able to survive
Cancer cells that do survive carry mutations and are thus less dependent on intercellular signaling for cell division and survival, and they may also escape apoptosis
As the tumor enlarges, self-perputuating mechanisms set in
Explain tumor angiogenesis
As a tumor enlarges, O2 demand increases
Internal cells become hypoxic
Hypoxic means there will be high levels of HIF (hypoxic inducing factor)
The tumor cells will then secrete VEGF in order for new capillaries to sprout and supply the tumor cell with more blood
Signaling between cancer and stromal cells (which are _______) evolve to help tumor survival
Stromal cells are the structural cells within a tumor
Tumor microenviornment is very important
Explain the three important genetic factors within cancer
- Oncogenes: “GOF”
- Tumor supressors: “LOF”
- Dna maintenance genes- maintain genomic stability
Oncogene: expression is ______
Derived from a _______ that is present in normal cells but becomes an oncogene when activated
Explain the ways oncogenes can get activated
Oncogene expression is causative
Oncogenes are derived from protooncogenes that are normally inactive but become oncogenes when activated
Oncogenes can be activated by mutations, gene amplification, or chromosome rearrangement
Explain the three scenarios:
Inserting Myc into a mouse strain
Inserting Ras into a mouse strain
Inserting Ras and Myc
Just myc: tumors will develop within about 100 days
Ras is more oncogenic, so it will start creating tumors more quickly
Ras and Myc together are very deletarious (activating more than one oncogene is very deadly)
They work together to become really cancerous
Explain the different mutations that arise to give Gain of Function vs loss of function
Gain of function (overactivity mutation):
Single mutation event can create an oncogene
Loss of function (underactivity mutation):
mutation even inactivates the tumor supressor gene on one chromosome (no effect of mutation in the other copy), it isn’t until a second mutation even that creates the problem: two inactivating mutations functionally eliminate the tumor supressor gene, promoting cell transformation
Loss of function: Tumor Supressor
Need to look for loss of gene
LOF is due to both ___ and ___ changes
Gene profiling is useful but complicated by ______
LOF: Tumor Supressor Genes
Need to look for loss of gene
LOF is due to both genetic and epigenetic changes
Gene profiling is useful but complicated by multiple contributing mutations
___ is one of the INK proteins involved in many types of cancer (Ink stands for___)
p16 is one of the INK proteins involved in many types of cancer (INK stands for INhibitor of cdK’s)
Explain how normally, active p16 is within a non-proliferating cell
And then how if p16 is inactive or absent, a cell can proliferate
Explain the mechanism
Normally, p16 is bound fo Cdk4, inhibiting it from becoming active and expressing S phase genes
When p16 is absent or inactive, Cdk4 can bind to its regulatory partner cyclinD, activating the Cdk4, allowing it to phosphorylated Rb, which then allows expression of S phase genes
