TY - JOUR
T1 - All-trans retinoic acid reverses phorbol ester resistance in a human myeloid leukemia cell line
AU - Yang, Kuender D.
AU - Mizobuchi, Tokihide
AU - Kharbanda, Surender M.
AU - Datta, Rakesh
AU - Huberman, Eliezer
AU - Kufe, Donald W.
AU - Stone, Richard M.
PY - 1994/1/15
Y1 - 1994/1/15
N2 - Treatment of human HL-60 leukemic cells with 12-O-tetradecanoylphorbol- 13-acetate (TPA) is associated with activation of protein kinase C (PKC) and induction of monocytic differentiation. An HL-60 variant cell line, termed HL-525, derived from long-term exposure to TPA (Homma et al, Proc Natl Acad Sci USA 83:7316, 1986) is resistant to TPA-induced differentiation and displays decreased PKCβ expression compared with the HL-60 parent line. However, this variant exhibits features of granulocytic differentiation, including nitroblue tetrazolium reduction, when exposed to all-trans retinoic acid (ATRA). Whereas treatment of HL-525 cells with ATRA or TPA alone had no effect on features of monocytic differentiation, these agents in combination resulted in cellular adhesion, nonspecific esterase staining, and induction of the c-fms (monocyte growth factor receptor) gene. In order to measure PKC expression associated with the reversal of TPA resistance by ATRA, we exposed HL-525 cells to ATRA and analyzed PKC-mRNA and protein levels. Exposure of HL-525 cells to ATRA for 3 days resulted in induction of PKCβ transcripts, whereas there was little change in PKCα mRNA levels. ATRA treatment was also associated with an increase in PKC activity and an induction of cytosolic PKCβ protein levels. These findings are consistent with the hypothesis that ATRA reverses TPA resistance in HL-525 cells by enhancing the expression of PKC.
AB - Treatment of human HL-60 leukemic cells with 12-O-tetradecanoylphorbol- 13-acetate (TPA) is associated with activation of protein kinase C (PKC) and induction of monocytic differentiation. An HL-60 variant cell line, termed HL-525, derived from long-term exposure to TPA (Homma et al, Proc Natl Acad Sci USA 83:7316, 1986) is resistant to TPA-induced differentiation and displays decreased PKCβ expression compared with the HL-60 parent line. However, this variant exhibits features of granulocytic differentiation, including nitroblue tetrazolium reduction, when exposed to all-trans retinoic acid (ATRA). Whereas treatment of HL-525 cells with ATRA or TPA alone had no effect on features of monocytic differentiation, these agents in combination resulted in cellular adhesion, nonspecific esterase staining, and induction of the c-fms (monocyte growth factor receptor) gene. In order to measure PKC expression associated with the reversal of TPA resistance by ATRA, we exposed HL-525 cells to ATRA and analyzed PKC-mRNA and protein levels. Exposure of HL-525 cells to ATRA for 3 days resulted in induction of PKCβ transcripts, whereas there was little change in PKCα mRNA levels. ATRA treatment was also associated with an increase in PKC activity and an induction of cytosolic PKCβ protein levels. These findings are consistent with the hypothesis that ATRA reverses TPA resistance in HL-525 cells by enhancing the expression of PKC.
UR - http://www.scopus.com/inward/record.url?scp=0028137667&partnerID=8YFLogxK
U2 - 10.1182/blood.v83.2.490.490
DO - 10.1182/blood.v83.2.490.490
M3 - 文章
C2 - 8286746
AN - SCOPUS:0028137667
SN - 0006-4971
VL - 83
SP - 490
EP - 496
JO - Blood
JF - Blood
IS - 2
ER -