Comparative responsiveness of HL-60, HL-60R, and HL-60R+ (LRARSN) cells to @entity1968 , XXXX , 9 cis-retinoic acid, and @entity11413 .

@entity10815 @entity3873 @entity17913 @entity11413 @entity4621 @entity865 @entity687 @entity1968 @entity554
In HL-60 cells, @entity1968 (RA) and 9 cis-RA induce granulocytic differentiation, and @entity3873 and @entity11413 induce monocytic differentiation. To study the role of @entity554 resistance on the response to these agents, we investigated their effects in HL-60 cells, @entity554 -resistant HL-60R cells, and HL-60R+ cells in which @entity554 sensitivity has been restored. In HL-60 cells, @entity10815 (ctsd) mRNA levels are increased by these agents and by cholera toxin after pretreatment with each agent. @entity3873 , 9 cis-RA, and @entity11413 increase @entity687 ( @entity687 ) mRNA expression, and pretreatment with these agents or RA potentiates the stimulation of @entity687 by @entity4621 ( @entity865 ). Pretreatment of HL-60 cells with all of the agents confers inducibility of @entity17913 (ctsl) mRNA by TPA in previously unresponsive cells. In HL-60R cells, none of the agents alone or in combination significantly enhances the expression of the ctsd, @entity687 , or ctsl mRNAs. @entity554 stimulation (either alone or in combination with the other agents) of the three mRNAs is partially restored in the HL-60R+ cells. @entity3873 does not alter the expression of any of these mRNAs, and only the stimulation of @entity687 mRNA by @entity11413 is recovered. Treatment with all of the agents inhibits proliferation and stimulates differentiation of the HL-60 cells. RA and @entity3873 are unable to inhibit proliferation of the HL-60R cells, whereas only @entity3873 fails to inhibit proliferation of the HL-60R+ cells. None of the agents induces differentiation in either the HL-60R or HL-60R+ cells. Therefore, the mutation of the RA receptor alpha is insufficient to account for the altered responses of the HL-60R cells, and there are likely defects in other signaling pathways in these cells. These cells may prove useful in examining the mechanism of cross-resistance between various differentiating agents.
