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Activity of retinoic acid receptor‐γ selectively binding retinoids alone and in combination with interferon‐γ in breast cancer cell lines
Author(s) -
Widschwendter Martin,
Daxenbichler Günter,
Culig Zoran,
Michel Serge,
Zeimet Alain G.,
Mörtl Manfred G.,
Widschwendter Andreas,
Marth Christian
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970502)71:3<497::aid-ijc31>3.0.co;2-a
Subject(s) - retinoid , retinoic acid , cancer research , retinoic acid receptor , transactivation , cell culture , biology , cell growth , breast cancer , cancer cell , cancer , tretinoin , biochemistry , transcription factor , gene , genetics
Retinoids modulate several cell functions and especially inhibit the growth of a wide variety of cells including breast cancer. Retinoic acid receptor‐γ (RAR‐γ) has been shown to mediate the antiproliferative activity of retinoids. To further test this hypothesis we examined the effects of different RAR‐γ 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‐γ (IFN‐γ) 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‐γ 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‐γ selectively binding retinoids are potent inhibitors of breast cancer cell proliferation, alone and in combination with IFN‐γ. For this reason and because of a possible low toxicity, as compared with retinoic acid, we speculate that these RAR‐γ selective binding retinoids might be of clinical importance. Int. J. Cancer 71:497‐503, 1997. © 1997 Wiley‐Liss Inc.