Growth Factorsint-2sis
Growth Factor ReceptorserbB-1fmskitmeterbB-2
Cytoplasmic Kinasessrcbcr-ablfeslckyes
Nuclear Proteinsetsfosjunmyc
FGFPDGF
EGF-RCSF-1RStem Cell GF-RHepatic GF-RHeregulin R
FAMOUS ONCOGENES
FAMILIAL CANCER SYNDROMES
Li-Fraumenip53
Deleted in PancreasSmad4
RetinoblastomaRb
Breast CancerBrca1,2
Wilms TumorWT1
Nonpolyposis ColonMSH2,MLH1
Neurofibromatosis 1,2NF1,NF2
von Hippel-LindauVHL
Adenomatous PolyposisAPC
MelanomaINK4a/ARF
Cowden DiseasePTEN
GorlinPTCH
Multiple Endocrine NeoplasiaMEN1
THE DEFINITION OF A TUMOR SUPPRESSOR
Classical Features:
1. Loss of function mutations2. Targeted allelic loss- Methylation or Deletion3. Inherited mutations that predispose to cancer4. Somatic mutation in spontaneous tumors5. Ability to inhibit transformed cells in vitro
SELECTIVE PRESSURE THROUGH STRESS
From environment:
-Low oxygen-Low nutrients-Radiation-Ligands
From self:
-Random mutant-ROS-Grow too fast
Dealing with it:
-Arrest/Senesce-Apoptosis
MUTATE
Understanding what translation is really all about
Growth signals
PI-3k/mTOR PathwayAnd
Regulators ofRibosome biogenesis 60S 40S
5’
AA
AA
AA
AA
AA-3’
UTR
UTR
Active translationRibosome biogenesis
rRNA synthesisrRNA processingrRNA export
PI3K
GFR
Akt
Rheb
Ras
mTOR
Tuberin/Hamartin
PTEN
Neurofibromin
Tuberous sclerosis complex
Neurofibromatosis type 1 (NF1)
Cowden Syndrome Lhermitte-Duclos
disease
S6KeIF4E
NPMARF p68
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