Signaling And Cancer

Question 1

Mitogens

Answer 1

Growth factors that cause or inhibit growth

EGF and PDGF (tyrosine kinase)
TGF beta (serine threonine)
Wnts

Question 2

Stimulatory growth factors

Answer 2

Use Ras pathway

PDGF and EGF

Question 3

Inhibitory Growth factors

Answer 3

Cdk inhibitors (p15, p16, p21)

Inhibit cell proliferation

TGFbeta (smad)

Question 4

Ras

Answer 4

Point mutations can occur in Ras or NF1 (inactivates Ras)

Question 5

Inhibition of cell cycle arrest

Answer 5

Akt (pI3K Akt pathway) inhibits cell cycle by activating Rheb, then Tor

Tor is an important regulator of cell size and cell cycle progression

Question 6

Tumor Suppressor genes

Answer 6

APC, BRCA1/2, CDKN2A, SMAD4, NF1, PTEN, Rb, TP53

Question 7

Protooncogene sites for mutations in signaling pathways

Answer 7

Amount of growth factor, receptor, signal transduction proteins, G proteins, nonreceptor protein kinase cascades, nuclear transcription factors

Question 8

Oncogenes

Answer 8

Growth factors (PDGF), receptors (TRK, ERBB2), plasma membrane GTP binding proteins (K/H/NRAS), nonreceptor protein kinases (BRAF, BCR-ABL), transcription factors (MYC, MYCL) cell cycle or apoptosis regulators (CYCD1, CDK4, BCL2, MDM2)

Question 9

APC and Wnt

Answer 9

APC gene encodes for Wnt signaling pathway

Mutations associated with familial adenomatous poyposis

beta catenin regulated by destruction complex, phosphorylated for destruction to inactivate Wnt pathway

Wnt proteins activate Frizzled, prevent destruction complex, so beta catenin can bind TCF transcription factor for cell proliferation