what are the 4 major groups of tumors?
carcinoma
sarcoma
leukemia/lymphoma
neuroblastoma
what does monoclonal mean?
all cells within a cancer descend from a single common progenitor cell.
aka. cell of origin
list the three genetic modifications that convert proto-oncogenes into oncogenes?
translocation/transposition
gene amplification and over expression
point mutation
define dysplasia?
abnormal development of cells within tissue or organs
how may cancer cells achieve immortalization?
all transformed cells
cells that emerge/survive from a crisis
list at least four phenotypic characteristics of cancer cells
do not stop dividing when they contact neighboring cell
cancer cells often have chromosomal abnormalities
cancer cells have a greatly reduced requirement for growth factors to sustain growth and proliferation
cancer cells are anchorage independent
what does the term metastasis mean?
spread of cancer to a distant site
what is loss of heterozygosity?
loss of normal function in one allele of a gene in which the other allele was already inactivated
how can a mutation in a single gene target multiple phenotypic characteristics at the same time?
mutation in a pleiotropic gene
what is the most likely explanation for a specific cancer (colon cancer) appearing in several members of the same family?
affected individuals have inherited a defective allele whose product interferes with mismatch repair
what is a "magic bullet" in cancer? is p53 a magic bullet?
a magic bullet is a drug that would kill cancer cells by specifically targeting only the difference between cancer cells and their normal counterparts.
how is apoptosis modified in cancer cells?
increasing inhibitors of p53, or silencing the activators
how can cancer cells access vital supply?
Angiogenesis
define malignancy
very infectious/ cancerous
mutations in the protein Rb can lead to cancer. how might this happen?
Rb helps stop cells from growing too quickly. If it is mutated it will likely be dysfunctional and allow rapid cell growth
how can a virus modify the cell cycle and induce cancer?
by mutating TSGs
what are the two molecular mechanisms required for tumor-suppressor activation?
increase of oncogenes
decrease of tumor suppressor gene
define hyperplasia?
abnormal increase in number of cells in a tissue without any obvious abnormality in the morphology of individual cells
explain the pleiotropically effect of mutated gene in cancer.
simultaneously inducing a large number of altered phenotypes
why is p53 considered a tumor suppressor protein?
because it can halt cell proliferation temporarily or initiate apoptosis
list several ways that a proto-oncogene can be activated to become an oncogene
translocation/transposition
gene amplification and over expression
point mutation
cancer is considered a progressive multi step disease, why?
because it requires 4-6 mutations to reach the tumor state. also, tumor-genesis progresses by clonal expansion in which increasingly abnormal clones of cells outgrow their less mutant neighbors
G proteins do not synthesize GTP from GDP + Pi. True or False
True
Signal transduction is initiated by the binding of ______________ to receptor molecules in the plasma membrane
signal molecules
multiple lipid derived messengers are produced in membranes. true/false
true
why are phosphorylation cascades a common feature of cellular signal transduction?
because they amplify the original signal
PLC's release soluble and lipid second messengers in response to diverse inputs. true/false
true
phospholipases D and A2 create other lipid second messengers. true/false
true
what is the description of an agonist?
agonists usually work by binding to the ligand binding site and promoting its active conformation
enzymes activated by calcium ion concentrations are usually regulated by binding to what?
calmodulin
All G proteins are enzymes. true/false
true
G proteins bind to both GTP and GDP, but not simultaneously. true/false
True
what is an autocrine signaling?
a form of cell signaling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on the same cell, leading to changes in the cell.
PI 3-kinase synthesized PIP3 to modulate cell shape and motility. true/ false
true
binding of a signaling molecule to a(n)___________ leads directly to a change in distribution of ions across the membrane
ligand gated ion channel/ligand binding domain
G proteins are phosphorylated by GTP. true/false
False
describe the mechanism of activation of heterotrimeric G proteins?
when the G alpha subunits binds GTP
what is the function of a protein phosphatase?
reverse the actions of protein kinases and dephosphorylates phosphoserine, phosphothreonine, and phosphotyrosine
G proteins change their shape when they release GDP and then bind to GTP. true/false
true
what are the steps occurring following binding of ligand to receptor tyrosine kinases?
receptor oligomerization and autophosphorylization
what is the source for cAMP?
Adenylyl Cyclase is the integral membrane protein that makes cAMP from ATP
why are serine threonine and tyrosine the only amino acids that can be phophorylated by protein kinases?
because they contain the proper functional group (OH) to accommodate phosphorylation
what is a paracrine signaling?
cell signals nearby cell
which amino acids can be phosphorylated by protein kinases?
Serine
Threonine
Tyrosine
the function of a protein phosphatase is to _____________?
Reverse the actions of protein kinases and dephophorylates phosphoserine, phosphothreonine, and phosphotyrosine
how does binding GTP control the activity of G proteins?
-GTP binds to G alpha subunit
-activates G-alpha subunit which allows another G-subunit to bind
-Galpha has a subunit which deactivates G-alpha subunit
Bound to G-alpha it is active
made into GDP it is inactive
which signaling molecules stimulates a rise in cytosolic cAMP in animal cells?
Adenylyl Cyclases are stimulated by G-alpha which synthesizes more cAMP
find examples of "positive feedback" in a cell
The output enhances the original stimulus
Ex: Child birth with increased oxytocin which speeds up contractions
Ex: Blood Clotting. platelets attract more platelets
what happens when a "G protein" cleaves GTP to GDP?
It deactivates the G-alpha subunit
Why does signaling through a peptide growth factor(such as epidermal growth factor) allow for more rapid responses in a cell than signaling through a steroid hormone such as estrogen?
...
which signaling molecules stimulates a rise in cytosolic Ca+2?
IP3
what is the source for this Ca+2 (where is it stored)?
Endoplasmic Reticulum
Inositol triphosphate is a product of which enzymes?
Phospholipase C's
(PLCs)
what makes adenylate cyclase a signaling protein?
when it is activated it causes a response with the secondary messengers cAMP
list the second messengers
cAMP
Ca
IP3
DAG
PIP3
cGMP
NO
The mitogen activated protein kinases (MAPKs) are among the most commonly used protein kinases in cells. they are often employed by the cell in protein kinase cascades, where MAP3K phophorylates and activate MAP2K, which in turn phophorylates MAPK. What a
it can introduce a threshold and bring in cooperative behavior to do signaling over a narrow range.
can provide multiple sites for modulatory inputs from other pathways.