Effects of PPAR and RXR ligands in semaphorin 6B gene expression of human MCF-7 breast cancer cells.
This study tests the hypothesis that the activators of peroxisome proliferator-activated receptors (PPARs) and 9-cis-retinoic acid receptor (RXR) regulate human semaphorin 6B (Sema6B) gene expression. The human MCF-7 breast adenocarcinoma cell line was chosen because it expresses Sema6B at a high level. The Sema6B mRNA level was analyzed by RT-PCR and the semaphorin 6B protein content was determined using a polyclonal antibody that we have produced and characterized. Treatments with fenofibrate (a PPARalpha activator) and troglitazone (a PPARgamma ligand) strongly decreased the Sema6B mRNA. The drop in Sema6B mRNA level and in protein content was more important when the treatment combined the action of fenofibrate or troglitazone and 9-cis-retinoic acid. On the other hand, no significant change was observed in the Sema6B mRNA and protein levels when the cells were exposed to the combined action of GW610742 (a PPARbeta activator) and 9-cis-retinoic acid. These data suggest that PPARalpha/RXR and PPARgamma/RXR heterodimers are involved in the regulation of Sema6B gene expression and open new perspectives concerning the participation of these nuclear receptors in cell recognition and migration.
Murad
Hossam
H
IFR 111/EA 3446, Peroxisome Proliferators, Faculty of Sciences, BP 239, 54506 Vandoeuvre-les-Nancy, France. Hossam.Murad@scbiol.uhp-nancy.fr
Collet
Philippe
P
Huin-Schohn
Cecile
C
Al-Makdissy
Nehmann
N
Kerjan
Geraldine
G
Chedotal
Alain
A
Donner
Mireille
M
Devignes
Marie Dominique
MD
Becuwe
Philippe
P
Schohn
Herve
H
Domenjoud
Lionel
L
Dauça
Michel
M
D006801:Humans; D000077556:Alitretinoin; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology; D019281:Dimerization; D011345:Fenofibrate / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D019073:HT29 Cells; D020014:K562 Cells; D047493:PPAR alpha / Q000819:agonists / Q000737:chemistry; D047495:PPAR gamma / Q000819:agonists / Q000737:chemistry; D047488:Retinoid X Receptors / Q000819:agonists / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D000077288:Troglitazone
D000077556:Alitretinoin; D002839:Chromans; D011345:Fenofibrate; C503394:GW 610742; D047493:PPAR alpha; D047495:PPAR gamma; D047488:Retinoid X Receptors; D012333:RNA, Messenger; C504081:SEMA6B protein, human; D039961:Semaphorins; D013844:Thiazoles; D045162:Thiazolidinediones; D014212:Tretinoin; D000077288:Troglitazone