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.