Estrogen-dependent regulation of PPAR-gamma signaling on collagen biosynthesis in adenocarcinoma endometrial cells.
The link between estrogen and metabolic developmental factors of endometrial carcinoma is well established. PPAR- gamma, (an important modulator of metabolism) and estrogen receptor belong to a family of nuclear hormone receptors that were shown to interact with each other. The interaction may affect transcriptional activity of these transcription factors. The anti-diabetic troglitazone (TGZ) is well known PPAR- gamma ligand. The effect of troglitazone-induced PPAR- gamma activation on estrogen-dependent stimulation of collagen biosynthesis was studied in the Ishikawa endometrial adenocarcinoma cell line. We have found that the presence of estrogen activity in growth medium (1nM) augmented collagen biosynthesis in the cells. An addition of PPAR- gamma agonists, as troglitazone or clofibrat to the growth medium induced inhibition of collagen biosynthesis. The inhibition was effective only when estrogen receptor was stimulated, since removal of estrogen receptor by ICI 182- 780-dependent degradation did not affect collagen biosynthesis. The mechanism of the inhibition was found at the level of NF-kB (known inhibitor of collagen gene expression) and MAPK signaling. PPAR- gamma ligands stimulated expression of NF-kB, while they inhibited expression of p-38 but not ERK1/ERK2. The data document for the first time that inhibitory effect of PPAR- gamma ligands on collagen biosynthesis in endometrial adenocarcinoma cells requires functional estrogen receptor.
Surazynski
A
A
Department of Medicinal Chemistry, Medical University of Bialystok, Bialystok, Poland.
Jarzabek
K
K
Miltyk
W
W
Wolczynski
S
S
Palka
J
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D047495:PPAR gamma / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
D002839:Chromans; D004967:Estrogens; D047495:PPAR gamma; D011960:Receptors, Estrogen; D045162:Thiazolidinediones; D003094:Collagen; D000077288:Troglitazone