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Selected Publication:
Widschwendter, M; Daxenbichler, G; Culig, Z; Michel, S; Zeimet, AG; Mörtl, MG; Widschwendter, A; Marth, C.
Activity of retinoic acid receptor-gamma selectively binding retinoids alone and in combination with interferon-gamma in breast cancer cell lines.
Int J Cancer. 1997; 71(3):497-504
Doi: 10.1002/(SICI)1097-0215(19970502)71:3<497::AID-IJC31>3.3.CO;2-4
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- Co-authors Med Uni Graz
- Mörtl Manfred Georg
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- Abstract:
- Retinoids modulate several cell functions and especially inhibit the growth of a wide variety of cells including breast cancer. Retinoic acid receptor-gamma (RAR-gamma) has been shown to mediate the antiproliferative activity of retinoids. To further test this hypothesis we examined the effects of different RAR-gamma selectively binding retinoids (CD2325, CD2247, CD666 and CD437) on breast cancer cell lines. With exception of CD2247, all retinoids inhibited proliferation of MCF-7, SKBR-3, T47D and ZR-75-1 breast cancer cell lines, similar to the natural compound all-trans retinoic acid (ATRA). In addition, all 4 compounds were able to act synergistically with interferon-gamma (IFN-gamma) in all breast cancer cell lines including the retinoid-resistant BT-20 and 734-B lines. In functional transactivation assays we demonstrated that only in the MCF-7 cell line, TPA-mediated AP-1 activity was suppressed only by ATRA and CD2325, whereas in SKBR-3, another RA-sensitive breast cancer cell line, it was not. The synergistic antiproliferative activity involving retinoids and IFN-gamma could not be explained by an enhanced anti-AP-1 activity. No correlation was found between expression of RARs and cellular retinoic acid binding proteins (CRABPs) and antiproliferative effects of the retinoids. RAR-gamma selectively binding retinoids are potent inhibitors of breast cancer cell proliferation, alone and in combination with IFN-gamma. For this reason and because of a possible low toxicity, as compared with retinoic acid, we speculate that these RAR-gamma selective binding retinoids might be of clinical importance.
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