BMP4- and RA-induced apoptosis is mediated through the activation of retinoic acid receptor alpha and gamma in P19 embryonal carcinoma cells.
Some growth factors, for example, members of the transforming growth factor-beta family, can induce apoptosis in a variety of cells. Retinoic acid (RA) also causes apoptosis in several malignant cell types. We have previously demonstrated that, although BMP2 or BMP4 cannot induce apoptosis alone, BMP2 or BMP4 and RA synergize to induce apoptosis in 95% of P19 embryonal carcinoma cells within 4 days of treatment. Such treatment also prevents neuronal differentiation of these cells. Retinoids exert their many effects through any of six distinct nuclear receptors. These retinoid-activated transcription factors directly regulate genes involved in cellular response such as apoptosis. Complete understanding of how BMP and RA specifically induce cell death requires identification of the retinoid receptors controlling apoptosis. By using receptor-selective retinoid agonists and antagonists, we have obtained evidence suggesting that activation of RAR alpha or gamma is sufficient to induce apoptosis in BMP4-treated cells.
Department of Biology, Pharmacology, University of South Florida, Tampa 33620, USA.
M A
MA
Glozak
M B
MB
Rogers
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002460:Cell Line; D054278:Embryonal Carcinoma Stem Cells; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists; D011503:Transglutaminases / Q000235:genetics; D000097768:Retinoic Acid Receptor gamma
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D011503:Transglutaminases; D000097768:Retinoic Acid Receptor gamma; C525810:Bmp4 protein, mouse; C000607072:Rara protein, mouse