Interaction of retinoic acid and interferon-alpha in breast cancer cell lines.
Retinoids and Interferons have been demonstrated to synergistically amplify the inhibition of proliferation in cultured breast cancer cells. Recently we reported that interferon-gamma (IFN-gamma) modulates the action of retinoic acid (RA): IFN-gamma increased expression of retinoic acid receptor-gamma (RAR-gamma) and suppressed the increase of retinoic acid binding protein type II (CRABP-II) expression. To improve the understanding of mechanism mediating synergism we extended our studies to the type I interferon-alpha. Synergistic inhibition of proliferation could be detected also by IFN-alpha and RA in BT-20 and SKBR-3 breast cancer cell lines but not in MCF-7 cells. Neither IFN-alpha nor any retinoid tested alone were able to increase RAR-gamma message, only the combination of both had this ability. In MCF-7 breast cancer cell lines the combination of any retinoid with IFN-alpha increased CRABP II expression level compared with the retinoids alone. In contrast with SKBR-3 and BT-20 cells a combination of ATRA with IFN-alpha markedly reduced ATRA mediated CRABP II induction. These results suggest that two factors may be responsible for synergistic action of RA and IFN-alpha: the inhibition of the CRABP II expression and an IFN-alpha/RA mediated upregulation of RAR-gamma.
Widschwendter
M
M
Department of Obstetrics and Gynecology, Innsbruck University Hospital, Austria.
Daxenbichler
G
G
Bachmair
F
F
Müller
E
E
Zeimet
A G
AG
Windbichler
G
G
Uhl-Steidl
M
M
Lang
T
T
Marth
C
C
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000096:biosynthesis; D014212:Tretinoin / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin