Biological Significance of Size Features Mating Segregation Predator/Prey Enlarged Roots/Store Water Longer Fish Swims Faster Size & Function Egg Sizes/Maturation Time Body Size/Surface-Mass/Body Temperature/ Metabolic Rates/Longevity Fixed Adult Size/Continue Growing Leave Sizes/?
Evolution Question: Why Did Animals Become Bigger Early And Are Now Getting Smaller? O2 Food Supply Land Area
Size Property Is Intrinsic to an Organ Primodium Graft Exchange Amblystoma tigrinum A. punctatum Twitty and Schwind, 1928 Proc. Soc. Exper. Bio. Med. 25:686
Lats Homologs Function as TS in Flies and Mice St John et al. 1999 Nature Genetics
Tumorigenesis Requires Deregulation of Size-Control Mechanism Tumor development requires increasing total mass Multiple tumor suppressors and oncogenes affect Mechanisms of size control Molecules participating in size-control could be targets for anti-cancer drugs Potter and Xu 2001
S6k Tor Akt (PKB) InR PI3K Tsc1Tsc2 Active Potter et al. Cell 2001 Potter et al. Nat Cell Bio 2002 Inoki et al. G & D 2003 PTEN Rapamycin S6K Tor Inactive Tsc1 PP Tsc2 TSC Pathway Provides A Basis for Therapeutic Intervention Rheb
Clinical Trails for TSC and LAM 2003 Kwiatkowski, Harvard; Yeung, U of W Clinical trails 2003.4 US: Drs. McCormack, Franz, Bissler England: Drs. Simpson and Kingswood Germany: Dr. Weinke Pathway conserved, S6K activated in patients TSC pathway and drug target TSC animal trial 2002-2003 Many groups 2001,2002 Potter & Xu