DF/HCC Program Affiliation

Prostate Cancer
Cancer Cell Biology

Research Abstract

We are interested in the regulation of cell differentiation and pathways of differentiation that can be used to force the maturation of human tumors. We have described the fucntion of a novel nuclear receptor, PPARgamma, that controls the differentiation of adipose cells. This transcription factor is also the functioning receptor of the thiazolidinedione (TZD) class of anti-diabetes drugs. Ligand activation of PPARgamma also derived from breast, prostate and colon. Our research is focused on pathways of differentiation induced by activation of PPARgamma in normal and malignant cells. In addition, we are interested in mutations acquired in the PPARgamma pathways during tumorigenesis.

Publications

• Girnun GD, Naseri E, Vafai SB, Qu L, Szwaya JD, Bronson R, Alberta JA, Spiegelman BM.Synergy between PPARgamma Ligands and Platinum-Based Drugs in Cancer.Cancer Cell 2007 May;11(5):395-406.
  17482130
• Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM.The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle.Cell Metab 2007 Jan;5(1):35-46.
  17189205
• St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jäger S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM.Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators.Cell 2006 Oct 20;127
  17055439
• Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM.Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation.Cell Metab 2006 May;3(5):333-41.
  16679291
• Rhee J, Ge H, Yang W, Fan M, Handschin C, Cooper M, Lin J, Li C, Spiegelman BM.Partnership of PGC-1{alpha} and HNF4{alpha} in the Regulation of Lipoprotein Metabolism.J Biol Chem 2006 May 26;281(21):14683-90.
  16574644
• Wang L, Liu J, Saha P, Huang J, Chan L, Spiegelman B, Moore DD.The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes.Cell Metab 2005 Oct;2(4):227-38.
  16213225
• Handschin C, Lin J, Rhee J, Peyer AK, Chin S, Wu PH, Meyer UA, Spiegelman BM.Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha.Cell 2005 Aug 26;122(4):505-15.
  16122419
• Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB.TAZ, a transcriptional modulator of mesenchymal stem cell differentiation.Science 2005 Aug 12;309(5737):1074-8.
  16099986
• Chen Z, Torrens JI, Anand A, Spiegelman BM, Friedman JM.Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms.Cell Metab 2005 Feb;1(2):93-106.
  16054051
• Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM.Transcriptional coactivator PGC-1 alpha controls the energy
  16054070
• Lin J, Handschin C, Spiegelman BM.Metabolic control through the PGC-1 family of transcription coactivators.Cell Metab 2005 Jun;1(6):361-70.
  16054085
• Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P.Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.Nature 2005 Mar 3;434(7029):113-8.
  15744310
• Lin J, Yang R, Tarr PT, Wu PH, Handschin C, Li S, Yang W, Pei L, Uldry M, Tontonoz P, Newgard CB, Spiegelman BM.Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP.Cell 2005 Jan 28;120(2):261-73.
  15680331
• Smith MR, Manola J, Kaufman DS, George D, Oh WK, Mueller E, Slovin S, Spiegelman B, Small E, Kantoff PW.Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radi
  15468186
• Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jäger S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM.Defects in adaptiv
  15454086
• Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM.Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expr
  15100410
• Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S.p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene.Mol Cell B
  15024092
• Fan M, Rhee J, St-Pierre J, Handschin C, Puigserver P, Lin J, Jäeger S, Erdjument-Bromage H, Tempst P, Spiegelman BM.Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK.Genes Dev 2
  14744933
• Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG.Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha.Mol Cell 2003 Nov;12(5):1137-49.
  14636573
• Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, de la Chapelle A, Spiegelman BM, Eng C.Loss-of-function mutations in PPAR gamma associated with human colon cancer.Mol Cell 1999 Jun;3(6):799-804.
  10394368
• Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S.Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma.Proc Natl Acad S
  10097144