Retinoid receptors: pathways of proliferation inhibition and apoptosis induction in breast cancer cell lines.
In this study we investigated the effects of several selective agonist retinoids (specific for RAR alpha, RAR beta, RAR gamma, and RXR alpha, respectively) on the proliferation and apoptosis of human breast cancer cell lines. All these retinoids inhibit proliferation through apoptosis induction, but with some differences among the tested molecules and the three cell lines. In particular, estrogen receptor positive (ER+) cells display a higher sensitivity to RARs selective compounds, the RAR alpha selective compound being the most effective agent, while estrogen receptor negative (ER-) cells show a greater responsiveness to the RXR alpha selective retinoid. In all tested cell lines a potent antiproliferative and apoptotic effect was also displayed by a high dose of the RAR gamma selective compound. The apoptosis induction is associated with bcl-2 down-regulation, while p53 expression is not modified by any retinoid. Only in one cell line (ZR-75.1), after RAR alpha selective retinoid treatment is there an induction of RAR beta: therefore not only RAR beta induction but also other mechanisms may contribute to the growth inhibitory effect of retinoids in tested breast cancer cell lines.
Pre-clinical Oncology Laboratory, Advanced Biotechnology Center (ABC), Genoa, Italy.
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Raffo
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Emionite
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Colucci
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Belmondo
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Moro
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Bollag
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Toma
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001565:Benzoates / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000970:Antineoplastic Agents; D001565:Benzoates; D019253:Proto-Oncogene Proteins c-bcl-2; C000607071:RARA protein, human; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C068073:Am 580