Cell Signaling (1)
Describe autocrine cell signaling
A cell will release a ligand that will leave the cell, and the ligand will bind to a receptor protein on the cell surface to activate a signal transduction pathway inside the cell.
Explain in detail how intracellular receptors work including describing the size and charge of the ligands
A small/ non-polar ligand will cross the phospholipid bilayer will enter into the cell and bind to the receptor inside the cell which will then elicit a transduction cascade that will lead to a cellular response.
What are the two main phases of the cell cycle, which phase does the cell spend majority of time in, and what are some key events that occur in those two phases.
1. Interphase and Mitosis
2. Cell spends majority of time during interphase.
3. During interphase cell grows in size, makes proteins, replicates it's DNA. Mitosis cell divides in that each daughter is identical with an equal distribution of the DNA
Daily Double-Do cancer cells spend more or less time in the cell cycle than normal cells? Explain
Less time because they ignore the checkpoints.
What are four treatments for cancer.
Chemo
radiation
surgery
CAR-T
Describe paracrine, endocrine and gap junctions
Paracrine - signaling between two neighbor cells one cell releases a ligand and then this ligand binds to a receptor on the other cell to elicit a response. Endocrine - signaling between two cells that are far apart one cell releases a ligand and then this ligand travels through the blood stream binds to a receptor on the other cell to elicit a response. gap junctions - connexin transmembrane protein connects to adjacent cells that will allow exchange of materials
What are two examples of second messengers.
Ca+, cyclic AMP, DAG
What are the three sub-phases of interphase and what are key events in each phase
1. G1- cell grows in size, makes proteins, makes organelles
2. S phase - DNA replication occurs
3. G2 - cell makes proteins such as spindle finers for mitosis.
What are the two proteins that make up the checkpoint proteins, and what are the purpose of the checkpoint proteins.
1. CDK/cyclin
2. To fix any mistakes before the cell proceeds to the next phase of the cell cycle, if the errors cannot be fixed then apoptosis will occur.
Provide two reasons why hypoxic tumors are more difficult to treat then normoxic tumors.
1. Most chemotherapy drug need oxygen to work properly, and since there is low oxygen in these regions this impedes these drugs working properly.
2. Since there is poor blood flow in hypoxic regions of tumors, it is difficult to deliver the drug there.
Describe the structure of the ECM and what are two functions of the ECM.
ECM is the connection between transmembrame proteins (such as integrin) with proteins outside the cell such as collagen, fibronectin, and proteoglycans. Functions of the ECM are 1. Anchor the cell 2. Cell signaling
Describe in detail how an ion- channel linked receptor is activated.
An ion acts as the ligand binds to the ion channel receptor and this will cause a conformational change in the ion channel linked receptor that will either open or close the chanel, therefore either allowing or preventing ions to enter or exit the cell.
Daily double -What is angiogenesis, and what are two reasons why angiogenesis is essential for the growth and development of a tumor.
1. Formation of blood vessels
2. Provides nutrients and oxygen for rapidly growing tumor, and required for metastasis of the tumor.
Explain how proto-oncogenes and tumor suppressors regulate cell division in normal cells, and explain how the dysregulation of these genes can lead to cancer.
Proto-oncogenes promote cell division, while tumor suppressors stop cell division. In normal cells there is a balance between the two. In cancer cells proto-oncogenes mutate into oncogenes, therefore promoting uncontrolled cell division, while tumor suppressors are mutated and as a result there is no signal for the cell to stop dividing.
Describe in detail how CAR-T works
T cells are removed from your body.
•Through gene therapy using a virus vector a copy of the gene that will code for a receptor that will recognize an antigen on the surface of the cancer cell is introduced.
•These recombinant T-cells are grown in the lab and tested to make sure they are expressing the receptor protein.
•While the recombinant T cells are being produced in the laboratory, lympho depleting chemotherapy is performed on the patient to deplete the remaining T cells.
•Through an IV the recombinant T-cells are reintroduced back into the patient, and they should be able to recognize the cancer cells and attack them.
What are the three steps in cell signaling and what happens in each step.
1. Reception - ligand (hormone, ion, growth factor) binds to the receptor.
2. Transduction is when binding of the ligand to the receptor protein leads to a series of steps inside the cell where one protein activates or represses another protein in a series.
3. Response - a change in cellular activity ( cell divides or stops dividing, enzyme active or inactive, gene turned on or off, etc.)
What are the two purposes of second messengers.
1. Amplification of the signal 2. Activate a variety of proteins to elicit multiple cellular responses.
Describe three ways abnormal estrogen receptor cell singalong can lead to breast cancer
• Excess production of estrogen ligand
•A mutation in the estrogen receptor that will cause it to be active even if the estrogen ligand is not bound to the estrogen receptor
•If the dimerized estrogen receptor is mutated or it attracts other proteins that lead to increased transcription rates of genes for cell proliferation.
Describe how androgen receptor cell signaling works in normal prostate cells.
Testosterone will enter the target cell and will be converted into DHT.
•DHT is the ligand that will bind to the Androgen receptor (AR).
•The DHT-AR complex will migrate to the nucleus and turn on genes for cellular proliferation.
Provide five treatments for breast cancer that is caused by over-activation of the estrogen receptor pathway
Hormonal therapy to reduce estrogen ligand.
•Competitive inhibitor to prevent the estrogen receptor from binding to the estrogen receptor.
•Design a drug that will target the over-active dimerized estrogen receptor to the proteasome.
•Prevent the dimerized estrogen receptor from entering the nucleus.
•Prevent the dimerized estrogen receptor from binding to it’s target genes so those genes cannot express the proteins for cell proliferation
1. Ligand binds to the the receptor and the RTK dimerize.
2. Once the RTK's dimerize autophosphoryl ation of the intracellular domains of the the tyrosine residue on each dimer subunit.
3. The phosphorylated tyrosine's will attract other proteins inside the cell and bind them and activate them by adding a phosphate group to these proteins. Since the phosphorylated RTK attracts many different proteins many different cellular responses are elicited.
Explain in detail how a G-protein linked receptor is activated.
1. A ligand binds to G-protein linked receptor. 2. When ligand binds to G-protein linked receptor this results in a conformation change that will result in the G-protein receptor will bind to the G protein and cause the G protein to exchange GDP for GTP. 3. When the G protein is bound to GTP it is active and activate enzymes that will produce second messengers such as cyclic AMP, IP3 which will cause Ca+2 from smooth ER which CA+2 act as a second messenger, DAG that will allow an amplification of the signal and activation of a lot of different proteins to elicit an array of responses
Describe how estrogen signaling works in normal breast cells.
Estrogen enters the target cell and is the ligand for the intracellular estrogen receptor.
•When estrogen binds to the estrogen receptor, two estrogen receptors that have the estrogen ligand attached to it and dimerize.
•The dimerized estrogen receptor will now leave the cytoplasm and enter the nucleus where it will turn on genes for cell proliferation
Provide five treatment scenarios for targeting the AR in prostate cancer.
Castration to remove testosterone.
•Inhibit the enzyme that inhibits the conversion of testosterone into DHT.
•
•Competitive inhibitor to prevent DHT from binding to AR.
•Design a drug that will target the over-active AR to the proteasome.
•Prevent the AR receptor from entering the nucleus.
•Prevent the AR from binding to it’s target genes so those genes cannot express the proteins for cell proliferation
Explain two reasons why using an angiogenesis inhibitor could be an effective treatment for certain cancers.
1. By cutting off blood flow tumor can not obtain oxygen and nutrients it needs to survive.
2. Tumors need blood vessels to metastasize, so by inhibiting angiogenesis could prevent metastasis.