Prospects for prevention and treatment of cancer with selective PPARγmodulators (SPARMs)

被引:133
作者
Sporn, MB [1 ]
Suh, N
Mangelsdorf, DJ
机构
[1] Dartmouth Coll Sch Med, Dept Pharmacol, Hanover, NH 03755 USA
[2] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA
关键词
D O I
10.1016/S1471-4914(01)02100-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear receptor and transcription factor that regulates the expression of many genes relevant to carcinogenesis, is now an important target for development of new drugs for the prevention and treatment of cancer. Deficient expression of PPAR gamma can be a significant risk factor for carcinogenesis, although in some cases overexpression enhances carcinogenesis. Ligands for PPAR gamma suppress breast carcinogenesis in experimental models and induce differentiation of human liposarcoma cells. By analogy to the selective estrogen receptor modulator (SERM) concept, it is suggested that selective PPAR gamma modulators (SPARMs), designed to have desired effects on specific genes and target tissues without undesirable effects on others, will be clinically important in the future for chemoprevention and chemotherapy of cancer.
引用
收藏
页码:395 / 400
页数:6
相关论文
共 75 条
[1]  
Alberts DS, 1999, CANCER RES, V59, P4743
[2]  
ANZANO MA, 1994, CANCER RES, V54, P4614
[3]  
ANZANO MA, 1994, CANCER RES, V54, P1653
[4]  
Bischoff ED, 1998, CANCER RES, V58, P479
[5]  
Camp HS, 1997, J BIOL CHEM, V272, P10811
[6]   Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial [J].
Cauley, JA ;
Norton, L ;
Lippman, ME ;
Eckert, S ;
Krueger, KA ;
Purdie, DW ;
Farrerons, J ;
Karasik, A ;
Mellstrom, D ;
Ng, KW ;
Stepan, JJ ;
Powles, TJ ;
Morrow, M ;
Costa, A ;
Silfen, SL ;
Walls, EL ;
Schmitt, H ;
Muchmore, DB ;
Jordan, VC .
BREAST CANCER RESEARCH AND TREATMENT, 2001, 65 (02) :125-134
[7]   A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis [J].
Chawla, A ;
Boisvert, WA ;
Lee, CH ;
Laffitte, BA ;
Barak, Y ;
Joseph, SB ;
Liao, D ;
Nagy, L ;
Edwards, PA ;
Curtiss, LK ;
Evans, RM ;
Tontonoz, P .
MOLECULAR CELL, 2001, 7 (01) :161-171
[8]   PPAR-γ dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation [J].
Chawla, A ;
Barak, Y ;
Nagy, L ;
Liao, D ;
Tontonoz, P ;
Evans, RM .
NATURE MEDICINE, 2001, 7 (01) :48-52
[9]   PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway [J].
Chinetti, G ;
Lestavel, S ;
Bocher, V ;
Remaley, AT ;
Neve, B ;
Torra, IP ;
Teissier, E ;
Minnich, A ;
Jaye, M ;
Duverger, N ;
Brewer, HB ;
Fruchart, JC ;
Clavey, V ;
Staels, B .
NATURE MEDICINE, 2001, 7 (01) :53-58
[10]   Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-γ and nuclear factor-κB [J].
Chung, SW ;
Kang, BY ;
Kim, SH ;
Pak, YK ;
Cho, D ;
Trinchieri, G ;
Kim, TS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (42) :32681-32687