Possible involvement of Bcl-2 pathway in retinoid X receptor alpha-induced apoptosis of HL-60 cells.
Retinoids induce granulocytic differentiation and subsequent apoptosis in human myeloid (HL-60) leukemia cells. Differentiation is induced due to activation of retinoic acid receptors (RARs) whereas, activation of retinoid X receptors (RXRs) seems to be essential for driving these cells into apoptosis. In order to understand the mechanism of RXR induced apoptosis, we used a variant HL-60 cell line (HL-60R) with a transdominant negative mutation. The retroviral vector-mediated gene transfer was used to introduce the functional RARs or RXR alpha into HL-60R cells. We studied the effect of receptor-selective retinoid treatment on the expression of Bcl-2 and Bax oncogenes by reverse-transcription polymerase chain reaction (RT-PCR) and immunoblot analysis in RARs and RXR alpha transfected HL-60 cells. Our results show that activation of RXR alpha results in apoptosis via down-modulation of Bcl-2 mRNA as well as its gene product expression with no change in Bax mRNA expression.
Agarwal
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Department of Anatomy and Cell Biology, University of North Texas Health Science Center and North Texas Eye Research Institute, Fort Worth 76107, USA. nagarwal@molly.hsc.unt.edu
Mehta
K
K
D000077556:Alitretinoin; D017209:Apoptosis; D018922:HL-60 Cells; D006801:Humans; D009154:Mutation; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012190:Retroviridae; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D000077556:Alitretinoin; D014212:Tretinoin