signal

Question 1

Activated Receptor tyrosine Kinase actions

Answer 1

Activated RTKs phos effector proteins and reveals docking site for adapter protein GRB2

Question 2

RTK phos of PLC

Answer 2

Breaks down membrane inositol phosphates to secondary messengers

IP3 to increased Ca (from ER) to act PKC

DAG to act PKC to act TFs

Question 3

RTK phos of PI3K

Answer 3

Phosphatidyl Inositol 3 Kinase phosphorylates membrane PLs

act PKB inhibs apop: PI3K to PKB/Akt to bcl-2 to inhib apop

Question 4

RTK revelation docking site

Answer 4

GRB2 to SOS (RAS GEF) to act GTP binding RAS to RAF to MEK to MAPK to act TFs (FOS, JUN) to MYC to Cyclin D to allowing cell cycle

Question 5

AKT/PKB

Answer 5

promotes cell cycle

GF to PI3K to PIP3 to Akt (phosphors inhibitors of bcl-2 allowing cell growth) to bcl2

PTEN inacts Akt therefore downregulating bcl-2

Question 6

HER fam of receptors

Answer 6

HER = human epidermal growth factor - forms heterodimers
HER2 does not have ligand binding domain (no GF rqrd) therefore always ready
HER1,3,4 requires signal GF to allow dimerization and allow TK activity

Question 7

EGF-R in cancers

Answer 7

EGF-R = HER (1,2,3,4). HER2 in 30% of breast cancers = very aggressive and unstable

Question 8

Inhib HER2

Answer 8

Herceptin = Trastuzumab = monoclonal Ab

Question 9

Targeting overexpressed GF (RTK)

Answer 9

Cetuximab - blocks EGFR binding sites
Gefitinib - blocks autophos of TK

Goal is to block RTK activation of MAPK = inhib cell prolif

Question 10

Targeting effectors of RTKs

Answer 10

Small G-protein RAS must be directed to PM to interact with GEF (SOS) to be activated. RAS anchored by farnesyl group (attached to N-term by farnesyl transferase). If farnesyl is inhibited then RAS is inhib.

Question 11

Farnesyl Transferase inhibitor

Answer 11

Tipifarnib and Lonafarnib

Question 12

TFs as protooncogenes

Answer 12

TransC of FOS and MYC enhanced upon GFR activation. FOS and MYC activate transC genes (ex:cyclin D) promoting cell cycle progression. Tumors increase these oncogenes. Sometimes upreg of MYC can bypass activation needed.

Question 13

Steroid Hormones

Answer 13

Lipid soluble, simple and kinase free. HR connects with chaperon until H binds and HR complex enters nucleus

Question 14

Breast Cancer and Estrogen

Answer 14

Some breast tumors rely on estrogen mediated transC activation for growth. After est/estradiol attaches to R = TF. ERE activated by HR complex and increases transC, particularily Cyclin D.
Can also have overexpression of signal cascade by increased estrogen receptor

Question 15

Est receptor antagonist

Answer 15

Tamoxifen = binds to estradiol site and inhibits activation of gene expression

Question 16

Prostate Cancer location

Answer 16

Primarily in periph zone; BPH in transition zone

Question 17

Prostate Cancer pathway

Answer 17

T to cell interacts with 5alpha-reductase to DHT to AR to dimer and phos to ARE to coact recruit to:

Increased PSA (serum marker for overactive AR signal and excess prolif), increased growth (cyclin D) and increased survival

Question 18

AR antagonist

Answer 18

Flutemide and bicalutamide = AR antagonist for H-sensitive prostate cancer