9-18 cancer II Flashcards Preview

MCBG EXAM 3 FINAL > 9-18 cancer II > Flashcards

Flashcards in 9-18 cancer II Deck (30):

A: What are the 6 common Characteristics for Cancerous Stem Cells

B: What cells are these CA Stem cells similar to?

1. LOTS of Telomerase Expression=immortality/self renewal
2. LOTS of ABC transporters=drug resistance

3. low Proliferation rates =drugs resistance to ones tht selectively target overprogressive CA

4. come from other CA stem cells OR normal stem cells with mutation or epigenetic chnges
5. NEED TGF-b and Wnt proteins from either autocrine or paracrine origins
6. TGFb and Wnt signaling induce tx-factors involved in making pluripotent stem cells

B: Stem cells and mesenchymal metastatic cells have overlapping phenotypes!


Explain the significance of Yamanakas discovery regarding pluripotent stem cells

discovered tx factors (Oct, KIf4, Sox2 and Myc) can be used to encourage fibroblast -->into becoming pluripotent stem cells!


What is a Cancer Stem Cell

2)What are the multiple ways these cells can come about? [4]

CA cells self-renew to make MORE bad stem cells AND simultaneously generate proliferating [non-stem cell tumor cells] ---> ex. [transit amplifying cells]

* can come from OTHER CA Stem Cells

* normal stem cells with sustained mutations

*proliferating differentiating [NON-stem cell CA cells] with mutations/epigenetic changes --> gives them stem cell properties

*[NON-stem cell CA cells] that are just induced by TGFb and Wnt signals


transit amplifying cells
2) What produces these cells?

[NON-stem cell tumor cell] that proliferates a lot and if mutation or epigenetic change allowing it to gain stem cell properties will become CA stem cell!<--tht will self-renew

Are produced by CA stem cells


EMT transition by invasive tumor cells is activated by _____ and ______.
2) Where do these factors that activate EMT transition come from? [3]

3)[T or F]These 2 factors can act by Canonical AND non-canonical pathways in transformed cells

EMT transition by invasive tumor cells is activated by extracellular TGFb and Wnt

2)TGFb and Wnt comes from
-activating proteases cleave pro-TGFb in ECM
-untransformed cells in tumors microenvironment secrete TGFb and Wnt

-Autocrine secretion from the tumor itself

3) TRUE!


Mesenchymal cells have a _____ phenotype. What happens when Wnt receptors are activated by Wnt ligands?

Mesenchymal cells have "stem cell-like" phenotypes.

*When Wnt receptors are activated in Mesenchymal cells
--->B-catenin is made which INC Myc and
DEC E-cadherin (cell-cell/cell-matrix adhesion lost)


TGFb has OPPOSITE effects when activated in normal cells vs. Transformed Tumor cells. What are they? [2]

B: Which one is considered "Canonical" ?

1) TGFb in Cancer Cells: --> [Oncogene]
*Activates Smad2/3 tx factor to upregulate genes that generate mesenchymal state
*Activates Ras-MAPK and Akt pathway-->proliferation & migration smh
2) TGFb in normal cells:
*Activate Smad2/3 tx factors but instead STOPS proliferation and migration ---->CANONICAL! [Tumor suppressor]


Activation of [Akt] typically leads to ____ ____

Akt Activation = Cell Survival!


What 4 events occur AFTER an EMT tumor cell transition?

EMT(epithelial-->mesenchymal transition) causes:

1. Cells PM loses E-Cadherin
2. Cells lose cell-cell/cell-ECM connection=acquire motility

3. AKT and RAS-MPK pathways are activated along w/Pluripotent tx factors like Slug, Snail and Myc

4. INC uPA and type 4 procollagenase protease secretion


Describe some phenotypic characteristics of a Mesenchymal Tumor Cell [4]

2) What MAINTAINS this crazy Mesenchymal state?

ºCytoskeleton disorganized
ºECM and integrin contacts are broken due to uPA & type 4 collagenase proteases
ºLoss in E-cadherins
ºno antimetastatic miRNA

2) TGFb and Wnt maintain this mesenchymal phenotype


____ Instability is an enabling Hallmark of Cancer!

**Describe this Instability and how it's a "catch 22"

Genomic Instability! = Deficiency in telomerase will lead to chromosomal instability while on the other hand..HIGH/OVERXPRESSION of Telomerase = iMMortality/CA


How the heck do heavily mutated normal cells survive long enough to become CA cells? [7 steps]

2) What would happen if telomerase was NOT ReActivated during this?

Self-renewal of epithelial cell by repeated division
-->telomeres eventually shorten and uncap---> (if p53 is lost and there's no cell cycle checkpoint) ---->mutant cell survives and divides some more---->Chromosome mutations & massive chromo damage--->somehow telomerase ReACtivated---->Chromo now partially stabilized and survives with many more mutations = CANCER

2)With no telomerase ReActivation CA cell DIES due to catastrophic genomic chromosome instability


Telomerase Activation in CA cells is considered to be an _____[early/LATE] event because.....

2) Why is this?

Telomerase Activation in CA cells is a LATE event because telomerase has to be in low levels during beginning of mutated CA cell production.

2) Telomerase has to be low in beginning BECAUSE CA wants cell to initially have genetic instability


Loss of p53 is ____[early/LATE] event in the CA production pathway

Loss of p53 is a LATE event in CA production path along with LATE activation of telomerase activation


What MAIN events lead to genetic instability? [3]

1. Low levels of telomerase activity
2. DNA repair malfunction
3. Mitotic Catastrophe due to inability to go thru anaphase checkpoint


CA cells typically have _____[#] mutations but MOST have NO effect. These are known as _______ _____

CA cells typically have 40-60 mutations but MOST have no effect = PASSENGER MUTATIONS


1) What are Driver Mutations?

2) There are a limited # of mutations that are "Driver Mutations". What are they? [3]

1) mutations that CAN create a cancerous cell and maintain a TRANSFORMED CA phenotype

*[Sp40-Lrge T-viral antigen] mutation = stops Rb AND
stops p53

*mutated RAS


Why is Cancer truly a function/dependent on Age?
2)Can cancer be caused by a Single mutation?

3) How do Scientist know this?

**This is because it takes time to develop enough Driver mutations that can create Transformed CA phenotypes

2)NO...mutagens/gateway mutations may initiate CA but it takes MANY Driver mutations

3)If only 1 single mutation were needed for CA than incidence would be completely INDEPENDENT of age


A) In normal epithelium, dividing cells are confined to the ____ ______

B) IN low-grade neoplasia, where are dividing cells found and how do the superficial cells look?

C) How do epithelial cells look in HIGH-grade neoplasia?

D) What brings about the 4th stage: TRUE MALIGNANCY

A) in normal epithelium, dividing cells are confined to basal layer
B) low-grade=dividing cells are in lower third of epithelium with superficial cells flat but in early incomplete differentiation

C) HIGH-grade = epithelial cells are HIGHLY proliferative and show DeFective differentiation

D) begins when cells destroy and move pass Type 4 collagen basal lamina= invasion


1) Cells within a tumor are HETEROGENEIC. What does this even mean?

2)How is this related to X-activation

HETEROGENEIC=Even though cells of a CA tumor all originate from a SINGLE abnormal parent cell, they all still have MULTIPLE phenotypes (some metastasize and some don't)

2)All Cells from 1 tumor are NOT MOSAICS (like normal tissue cells)..and all have the SAME X-inactivation = means they come from single abnormal parent


Why do the Heterogeneic Tumor cells all have multiple phenotypes?

Even though all cells of 1 tumor come from same abnormal parent cell they all have DIFFERENT genetic and/or epigenetic differences = multiple phenotypes


Cancer Development are typically started by _____ _____ and promoted by ____ _____(which happens to be ____)

2)Explain how Carcinogenesis has a strict "pattern" to which the above events must be ordered?
"Cancer will only occur if......." [3]

Cancer Development typically started by mutagenic/gateway exposure and promoted by tumor promoters ( which are NON-mutagenic)

2) Cancer will only occur if...
A: [Mutagen/gateway mutation] INitiates FIRST and then is followed by promoter like expansion

B: Intensity of promoter after initiating gateway mutation reaches certain threshold (can't be too spaced out)
C: Cell is exposed to multiple events of a [mutagen/gateway initiator]


Why do tumor promoters which are NON-_____ end up leading to even further mutated cancerous cells?

2)What are some examples of tumor promoters? [3]

tumor promoters (NON-mutagenic) can expand the population of mutated cells --->INC chance a new mutation will occur in that population

2) GROWTH FACTORS such as general Cell expansion, estrogen/testosterone , Inflammation


How are Geographical Locations and CA incidence/exposure rates related?
2) Give an example?

Incidence of CA depends on where you're at and what environment/culture you partarke in.

2) If GA has a high incidence of Prostate CA in blacks, then a Af-American moving from Chicago to ATL will have then higher exposure/chance of acquiring Prostate CA


Good Diet with fruits and vegetables prevents ____% of CA while smoking cigarettes is attributed to _____% of all Lung CA

Good Diet can prevent 35% of CA while 90% of all Lung CA comes from Smoking Cigarettes!


Smad4 is a _____ gene which ____ TGFb pathway

Smad4 is a tumor suppressor gene which BLOCKS TGFb cancerous pathway


What does Apc do?

2)What happens when you lose Apc

3) Which 3 genetic abnormalities are MOST common in colorectal cancer cells?

[Apc] (note the lower case pc) suppresses B-catenin in the Wnt pathway which makes [Apc] a Tumor Suppressor Gene

2)When lost (usually early in process) this serves as an initiating/gateway mutation for CA

3) 1st: APC mutation / 2nd: p53 mutation / 3rd: Ras mutations


Ras and B-catenin are ____[oncogene/Tumor Suppresor genes]

Ras and B-catenin are BOTH ONCOGENES/Promote CA


What methods can you use to determine all genes expressed in a cell or tumor [2]

DNA array and Proteomic analysis can do this IN A SINGLE ASSAY!


Describe Proteomic analysis and how does it work? [2]

* 1 of the 2 ways you determine ALL genes expressed in a cell or tumor USING A SINGLE ASSAY

*shows exact phenotype using protein expression of a specific cancer and compares to normal tissue
----->allows u to classify the CA and fill requirement for specific tx tht are based on oncogene and tumor suppressor gene makeup