Differentiation and reversal of malignant changes in colon cancer through PPARgamma.
PPARgamma is a nuclear receptor that has a dominant regulatory role in differentiation of cells of the adipose lineage, and has recently been shown to be expressed in the colon. We show here that PPARgamma is expressed at high levels in both well- and poorly-differentiated adenocarcinomas, in normal colonic mucosa and in human colon cancer cell lines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased expression of carcinoembryonic antigen and the reversal of many gene expression events specifically associated with colon cancer. Transplantable tumors derived from human colon cancer cells show a significant reduction of growth when mice are treated with troglitazone, a PPARgamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPARgamma.
Sarraf
P
P
Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mueller
E
E
Jones
D
D
King
F J
FJ
DeAngelo
D J
DJ
Partridge
J B
JB
Holden
S A
SA
Chen
L B
LB
Singer
S
S
Fletcher
C
C
Spiegelman
B M
BM
D000230:Adenocarcinoma / Q000503:physiopathology*; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002839:Chromans / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000503:physiopathology*; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
D002839:Chromans; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone