Effects of retinoids and interferon-gamma on cultured breast cancer cells in comparison with tumor necrosis factor alpha.
The combination of retinoic acid or tumor necrosis factor alpha (TNF-alpha) with interferon gamma (IFN-gamma) resulted in a synergistic amplification of the anti-proliferative effect of IFN-gamma on cultured breast cancer cells. Retinoic acid could be replaced by other biologically active retinoids. This synergism was also observed for the induction of 2'-5'-oligoadenylate-synthetase, an enzyme which is not expressed constitutively on BT-20 human breast cancer cells and not inducible by retinoic acid or TNF-alpha alone. However, both substances augmented the IFN-gamma-mediated expression. On the other hand, only TNF-alpha and not retinoic acid was able to increase the IFN-gamma induced expression of HLA-DR on the cell surface. Both cytokines antagonized the IFN-gamma effect on detachability of cultured BT-20 cells. The combinations of retinoic acid with IFN-gamma increased the down-regulation of specific binding sites for 125I-IFN-gamma. On the other hand, IFN-gamma exerted no effect on the concentration of the cytoplasmic binding protein for retinoic acid. Data obtained in this study demonstrate a different pattern of action between retinoic acid and TNF-alpha regarding their synergism in combination with IFN-gamma.
Marth
C
C
Department of Obstetrics and Gynecology, University Hospital of Innsbruck, Austria.
Zech
J
J
Böck
G
G
Mayer
I
I
Daxenbichler
G
G
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000032:analysis; D017471:Receptors, Interferon; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D012176:Retinoids; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase