Term
| What must occur to lead to a complete loss of growth control? |
|
Definition
|
|
Term
| If a mutation is inherited, the risk of developing the malignancy is? |
|
Definition
|
|
Term
|
Definition
| epithelial cells- environmental damages are likely the cause |
|
|
Term
|
Definition
| supporting tissues of the body |
|
|
Term
| Cancer of the lung, stomach, skin and colon are? |
|
Definition
|
|
Term
| Cancer of the bone, blood vessels, and muscle are? |
|
Definition
| Sarcomas-such as osteosarcoma or rhabdomyosarcoma |
|
|
Term
| Cancer of the stem cells or bone marrow are? |
|
Definition
| Leukemias- such a lymphomas |
|
|
Term
| What is the problem with tumors? |
|
Definition
| Cell growing rapidly, not performing differentiated functions and they impinge on other tissues. |
|
|
Term
| What are two common treatments of tumors? |
|
Definition
1) Remove(surgery)
2) chemotherapy- most interfere with DNA synthesis...however they destroy normal cells as well resulting in hair loss, digestive problems(any normal cells with rapid turnover are affected the most) |
|
|
Term
| What life period is skipped by tumors when compared to normal cells? |
|
Definition
| senescence- after so many cell cycles most of the tissues die and then a few survivors regrow, tumors skip this stage altogether |
|
|
Term
| What type of cells need more serum normal or trnasformed? |
|
Definition
| Normal, they need 10%; transformed need <1% |
|
|
Term
| What is the difference between normal and transformed cells in the expression of LETS(fibronectin)? |
|
Definition
Normal-High
Transformed- Low |
|
|
Term
| What is the difference between normal and transformed cells in agglutinated lectins? |
|
Definition
Normal- No
Transformed- Yes |
|
|
Term
| What is the difference between normal and transformed cells when comparing forms of carbohydrates on the cell surface? |
|
Definition
Normal- normal
Transformed- Fetal forms |
|
|
Term
| What is the difference between normal and transformed cells in enzyme expression? |
|
Definition
Normal- adult
Transformed- fetal isozyme |
|
|
Term
| What type of cell will grow on top of each other? |
|
Definition
Transformed
Normal-want to communicate and will grow in one layer in a petri in a cobblestone appearance |
|
|
Term
| What are some of the differences seen in transformed cells(5)? |
|
Definition
1) Go is ignored as the cells cycle
2) G1 transit time is reduced when compared to non-transformed cells
3) Cells form multilayers; cell death via lack of nutrients
4) Reduced serum requirements for growth
5) Cell shape altered, cells less adherent to substrata, more rounded (reduced anchorage dependence) |
|
|
Term
| What does the serum provide? |
|
Definition
| Growth factors that tell the cells to proliferate, so transformed cells don't need factors to tell them to grow. |
|
|
Term
| A cell's response to a growth factor is determined by? Give me some examples of this... |
|
Definition
It is determined by whether the cell expresses the receptor for that growth factor
Examples...
1) response to glucagon
a-muscle-no receptors=no response
b-liver-contains receptor= response
2) Response to Insulin
a-muscle-contains receptor= response
b-liver-contains receptor= response |
|
|
Term
| Tell me more about growth factors... |
|
Definition
1) small proteins that stimulate a cell to grow and differentiate
2) can replace serum in order for cells to grow
3) stimulates a cell through a series of events known as SIGNAL TRANSDUCTION
4) Very important in development and differentiation
5) Molecular weight can range from 6,000 to 32,000 |
|
|
Term
EGF
1) What does it stand for?
2) What is its molecular weight?
3) What is its active concentration?
4) What are its target cells? |
|
Definition
1) Epidermal growth factor
2) 6045
3) 2-5 ng/ml
4) Fibroblasts, Glial cells, Hepatocytes, and SMC(smooth muscle cells) |
|
|
Term
PDGF
1) What does it stand for?
2) What is its molecular weight?
3) What is its active concentration?
4) What are its target cells? |
|
Definition
1) Platelet-derived growth factor
2) 32,000
3) 2-5 ng/ml
4) Fibroblasts, Glial cells, SMC |
|
|
Term
FGF
1) What does it stand for?
2) What is its molecular weight?
3) What is its active concentration?
4) What are its target cells? |
|
Definition
1) Fibroblast growth factor
2) 15,000
3) 10-15 pg/ml
4) Fibroblasts, Endothelial cells, Neuronal precursors |
|
|
Term
NGF
1) What does it stand for?
2) What is its molecular weight?
3) What is its active concentration?
4) What are its target cells? |
|
Definition
1) Nerve growth factor
2) 26,000
3) 5-10 ng/ml
4) Nuerons |
|
|
Term
TGF-a(alpha)
1) What does it stand for?
2) What is its molecular weight?
3) What is its active concentration?
4) What are its target cells? |
|
Definition
1) Transforming growth factor-a(alpha)
2) 6-10,000
3) 2-5 ng/ml
4) Fibroblasts, Glial cells, SMC, Hepatocytes |
|
|
Term
TGF-ß
1) What does it stand for?
2) What is its molecular weight?
3) What is its active concentration?
4) What are its target cells? |
|
Definition
1) Transforming Growth Factor-ß
2) 25,000
3) 1-5 ng/ml
4) Everything |
|
|
Term
| Pertaining to hormones and the glands that make and secrete them into the bloodstream through which they travel to affect distant organs. |
|
Definition
|
|
Term
| Of or relating to a hormone or to a secretion released by (endocrine) cells into the adjacent cells or surrounding tissue rather than into the bloodstream. |
|
Definition
|
|
Term
| Of, relating to, or being a substance that acts on surface receptors of the same cell that produced it. |
|
Definition
|
|
Term
| All of the growth factor receptors except TGF-ß have this type of domain? |
|
Definition
|
|
Term
| TGF-ß has this type of Domain? |
|
Definition
|
|
Term
| What is necessary for signal transduction? |
|
Definition
|
|
Term
| All of the information for growth stimulation resides in? |
|
Definition
| It is in the receptor, not the growth factor |
|
|
Term
| What are some of the early responses to growth factors? |
|
Definition
1) Turnover of PI
2) Increase in levels of intracellular Ca
3) Activation of Protein Kinase C
4) Formation of receptor-substrate complexes due to tyrosine phosphorylation
5) Activation of gene transcription |
|
|
Term
| What stimulates Protein Kinase C? |
|
Definition
|
|
Term
| What stimulates free calcium release from bound stores in the ER? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| It block inositol and CDP-DG from forming PI. |
|
|
Term
| What brings Ca from the outside? |
|
Definition
|
|
Term
| What brings Ca from the ER? |
|
Definition
|
|
Term
| Why do multiple growth factor receptors cluster together? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Do all GF's need to increase intracellular free calcium levels? |
|
Definition
No, for instane FGF doesn't.
But, PDGF and EGF do. |
|
|
Term
| What does an antibody to PIP2 do? |
|
Definition
-Blocks hydrolysis and formation of IP3
-Blocks PDGF and EGF mitogenesis
-No effect on FGF-induced mitogenesis |
|
|
Term
| What two types of compounds are required to generate animal tumors? |
|
Definition
1) initiators
2) Promoters |
|
|
Term
| What do tumor promoters activate? |
|
Definition
| Protein Kinase C (large lipleic proteins that don't turnover frequently |
|
|
Term
| What are the three classification of growth factors? |
|
Definition
1) early
2) intermediate
3) late |
|
|
Term
| What is phosphorylated on tyrosine, threonine, and serine residues? |
|
Definition
|
|
Term
| What enzyme can phosphorylate all of the residues for the MAPK to be activated? |
|
Definition
| MAP Kinases Kinase (also called MEK, for MAPK/ERK kinase) |
|
|
Term
| What activates MAP Kinase Kinase? |
|
Definition
| Phosphorylation by MAP Kinase Kinase Kinase (MAPKKK) |
|
|
Term
| What is an example of a MAPKKK? |
|
Definition
|
|
Term
| In order for raf to be fully activated it requires? |
|
Definition
|
|
Term
| What is a GTP binding protein that is similar to the alpha subunit of G proteins? |
|
Definition
|
|
Term
|
Definition
It will bind GTP and interact with phosphorylated raf to fully activate it by translocating to the membrane
Side note-while it is similar to the alpha subunit of G proteins, it does not activate adenylate cyclase |
|
|
Term
|
Definition
| Either tyrosine kinase receptors or by G-protein linked receptors |
|
|
Term
| What does GRB2 stand for and what does it do? |
|
Definition
-Growth factor receptor binding protein 2
-binds to growth factor receptors and acts as a bridge for SOS binding; GRB2 binds to phosphotyrosine residues through SH2 domains |
|
|
Term
| What does SOS do? What does it do? |
|
Definition
-Guanine nucleotide exchange factor
-SOS binds to GRB2, it is active and facilitates the exchange of GTP for GDP on ras |
|
|
Term
| What does GAP stand for? What does it do? |
|
Definition
-GTPase activating protein
-It antagonizes SOS activity |
|
|
Term
| Which Cyclin is active during G1? |
|
Definition
|
|
Term
| Which cyclin(s) are active during S phase? |
|
Definition
|
|
Term
| What is active during G2, which leads to M? |
|
Definition
|
|
Term
| What is a serine/threonine kinase, which phosphorylates nuclear proteins and allows cell division to occur? |
|
Definition
|
|
Term
| What forms a complex with p34cdc2 (it is synthesized in a cyclical pattern during the cell cycle)? |
|
Definition
|
|
Term
| What is a kinase which phosphorylates and inactivates p34cdc2? |
|
Definition
|
|
Term
| What also phosphorylates and inactivates p34cdc2 at an activity site? |
|
Definition
| CAK (CDK-activating kinase) |
|
|
Term
| What is a phosphatase which dephosphorylates p34cdc2 at two sites and activates its kinase activity? |
|
Definition
|
|
Term
When this happens, what do we call this...
-Cells swell
-Mitochondria dilate
-Organelles dissolve
-Plasma Membrane ruptures, releasing cytoplasmic material
-Inflammatory response frequently results |
|
Definition
|
|
Term
When this happens, what do we call this...
-Cell shrinks
-Chromatin condenses
-Nucleus fragments
-Cell breaks into membrane enclosed vesicles
-Phagocytosis results (PS a marker)
-No inflammatory response |
|
Definition
| Apoptosis-regulated cell death |
|
|
Term
| If a mutation leads to an inability to undergo apoptosis, what happens? |
|
Definition
| Cells with damaged DNA can proliferate, increasing the rate of mutation, and the probability of developing a neoplastic cell. |
|
|
Term
| What are the three phases of apoptosis? |
|
Definition
1) Initiation phase
2) signal integration phase
3) Execution phase |
|
|
Term
| What happens in the Initiation phase? |
|
Definition
-Death receptors(tumor necrosis factor receptor)
-Deprivation of growth factors(lack of positive signaling blocks anti-apoptotic factors from working)
-DNA damage
-Mitochondrial integrity (oxygen deprivation, radiation) |
|
|
Term
| What protein family consists of both pro-apoptotic and anti-apoptotic factors? |
|
Definition
|
|
Term
| When apoptosis is initiated, it is due to these proteases called? |
|
Definition
|
|
Term
| What leads to the activation of CAD, caspase-activated DNAse, destroying kinases and lamins)? |
|
Definition
| Execution caspases-they carry out most of the work leading to cell death |
|
|
Term
| What are the two ways to bring about apoptosis? |
|
Definition
| Activate death receptor or compromise mitochondrial integrity |
|
|
Term
| What do death signals include? |
|
Definition
1 )growth factor withdrawal
2) Cell injury
3) Steroids
4) High cytoplasmic Ca2+ |
|
|
Term
|
Definition
| Pro-apoptotic protease activating factor |
|
|
Term
| Bcl-2, Bcl-x, and Bcl-w are examples of? |
|
Definition
-Anti-apoptotic factors
-They can insert in outer mitochondrial membrane and antagonize channel forming pro-apoptotic factors
-Can bind cytoplasmic apaf and prevent it from forming the apoptosome |
|
|
Term
|
Definition
| It is a pro-apoptotic factor, that does ion channel forming. It allows cytochrome C to leave the mitochondria more easily. |
|
|
Term
| What is Bid and what does it do? |
|
Definition
| It is a pro-apoptotic factor (BH3 domain only), it can bind to channel formers, but cannot form channel on its own. |
|
|
Term
| What is similar to anti-apoptotic factors, but cannot bind to apaf? It will dimerize with BH3-only pro-apoptotic factors in outer mitochondrial membrane to form an ion channel which promotes cytochrome c release. |
|
Definition
|
|
Term
| What when activated, dimerize with channel forming factors also binds to anti-apoptotic factors to block their binding with apaf, so the apoptosome can form? |
|
Definition
|
|
Term
| What is the protein required for forming structural core of the (retro)virus? |
|
Definition
|
|
Term
| What is the envelope glycoprotein found in the membrane of the retorvirus? |
|
Definition
|
|
Term
| What is the reverse transcriptase, to convert RNA genome into dsDNA copy, which integrates randomly into the host chromosome? |
|
Definition
|
|
Term
| What is the receptor for the colony stimulating factor-1? |
|
Definition
|
|
Term
| What are the receptors for members of the FGF family? |
|
Definition
|
|
Term
| What is a receptor for the stem cell factor? |
|
Definition
|
|
Term
| What is a receptor for hepatocyte growth factor? |
|
Definition
|
|
Term
| What is a receptor for thrombopoeitin? |
|
Definition
|
|
Term
|
Definition
| transcription factor activated by MAP kinase |
|
|
Term
| What is the Insulin signaling pathways? |
|
Definition
1) phosphorylate...IRS-1
2) form GRB2:IRS-1complex
3) form SOS:GRB2:IRS-1 complex
4) activates Ras-GDP to Ras-GTP
5) activates raf kinase
6) eventually activates MAP kinase(ERK) and ISPK(Insulin stimulated protein kinase) |
|
|
Term
| What protein also phosphorylates p34cdc2 at an inactivation site? |
|
Definition
|
|
Term
What is a caspase?
Where does it cleave? |
|
Definition
Cysteine protease (catalytic triad with a cysteine at the active site)
It cleaves next to aspartate residues in target proteins |
|
|
Term
| What does FADD stand for? |
|
Definition
| Fas associated death domain protein (fas is membrane-bound ligand which binds to death domain receptors) |
|
|
Term
| How do growth factors block apoptosis? |
|
Definition
1) PDGF- binds to receptor and activates PI-3 kinase
2) PI-3 kinase activation leads to the phosphorylation and activation of PKB(AKT) via PDK-1
3) AKT phosphorylates and inactivates BAD (BH-3 only pro-apoptotic factor)
4) MAP kinase kinase phosphorylates the protein kinase RSK, and activates it
5) RSK also phosphorylates BAD, to inactivate it |
|
|
Term
|
Definition
| BH-3 only pro-apoptotic factor protein |
|
|
Term
| What happens when you have a mutated Bcl-2? |
|
Definition
| Over-expression tips balance to anti-apoptosis, and mutations accumulate when DNA is damaged. Bcl-2 also transport drugs out of cells, so when over-expressed, they will block chemotherapy |
|
|
Term
|
Definition
|
|
Term
| Where are many miRNA genes located? |
|
Definition
| in introns of other genes |
|
|
Term
| What happens if miRNA is always expresse? |
|
Definition
| Can act as an oncogene and ablate the activity of a protein which regulates cell growth; thus getting uncontrolled cell proliferation |
|
|
Term
| If you lose the expression of miRNA? |
|
Definition
| Can act as a tumor supressor, a growth stimulatory gene may be constitutively expressed. |
|
|
Term
| What are tyrosine kinase viral oncogenes located on the membrane? |
|
Definition
|
|
Term
| What is a growth factor viral oncogene and its located in the cytoplasm? |
|
Definition
|
|
Term
| What is a GTP-binding protein viral oncogene and its located in the membrane or cytoplasm? |
|
Definition
|
|
Term
| What is a serine/threonine kinase viral oncogene located on the membrane or cytoplasm? |
|
Definition
|
|
Term
| What is a transcription factor viral oncogene located in the nucleus? |
|
Definition
|
|
Term
| What happens with mutated c-raf? |
|
Definition
Leads to an improper activation of MAPK
-Mutated raf is active without ras
-Mutated raf kinase activity is constitutive
- Mutated such that raf is over-expressed
Improper activation of MAPK would lead to initiation of cell growth at improper times |
|
|
Term
| What mutations lead to autocrine stimulation? |
|
Definition
|
|
Term
| What are transcription factors that can be oncogenes if altered form exists, inappropriate expression, or increased or decreased ability to bind DNA also will affect cell growth? |
|
Definition
1) fos
2) myc
3) jun
4) max
5) ski
6) min
7) myb
Fos(tered) Myc(el) Jun(berg) Max(amizes) Ski(ing) Min(us) Myb(e the summer) |
|
|
Term
| What has lost its GTPase activity and what does this mean? |
|
Definition
v-ras
-Ras protein is constitutively active
-GAP cannot activate GTPase activity in v-ras |
|
|
Term
| Normal cells can be transformed by the introduction of either c-ras or v-ras by over-expression, how do they differ though? |
|
Definition
-GAP can overcome transformation by c-ras
-GAP cannot overcome transformation by v-ras |
|
|
Term
| What regulates the E2F family of transcription factors? |
|
Definition
|
|
Term
|
Definition
| Binds to E2F and blocks transcription of genes required for the G1 to S cell cycle transition |
|
|
Term
| What happens when Rb is phosphorylated? |
|
Definition
| It dissociates from E2F, and transcription is initiated so cells can enter the S phase |
|
|
Term
| What regulates Rb phosphorylation such that Rb is only phosphorylated at a specific point in the cell cycle? |
|
Definition
| cyclin complexes (cdk2 and cyclin A) |
|
|
Term
|
Definition
| This regulatory step at the G1/S boundary is missing and cell proliferation will result. |
|
|
Term
|
Definition
1) Recognizes DNA damage, then activating p53 transcription factor activity
2) p53 stimulates the transcription of GADD45 which repairs the damaged DNA
3) p53 stimulates the transcription of p21 (a cyclin kinase inhibitor, CKI) which blocks cdk-dependent phosphorylation of Rb, thus arresting cells in the cell cycle
4) if damage cannot be repaired, apoptosis-promoting genes are transcribed |
|
|
Term
| Loss of some miRNA expression can lead to overexpression of? |
|
Definition
| Bcl-2 and ras leading to cancer, hence miRNA defects are oncogenes |
|
|
