Influence of RARalpha gene on MDR1 expression and P-glycoprotein function in human leukemic cells.
BACKGROUND
Multidrug resistance (MDR) phenotype of malignant cells is the major problem in the chemotherapy of neoplasia. The treatment of leukemia with retinoids is aimed on the induction of leukemic cells differentiation. However the interconnections between retinoid regulated differentiation of leukemic cells and regulation of MDR remains unclear.


METHODS
Four lines of cultured leukemic cells of diverse types of differentiation were infected with RARalpha gene and stable transfectants were isolated. We investigated the differentiation of these cells as well as the expression of RARalpha and MDR1 genes and P-glycoprotein (Pgp, MDR protein) functional activity in these cells.


RESULTS
All RARalpha transfected sublines demonstrated the increase in the quantity of RARalpha mRNA. All these sublines became more differentiated. Intrinsic activity of MDR1 gene (but not Pgp functional activity) was increased in one of the transfectants. All-trans-retinoic acid (ATRA) induced Pgp activity in two of three infectants to a larger extent than in parental cells.


CONCLUSIONS
The data show that RARalpha regulates MDR1/ Pgp activity in human leukemic cells, in the first place, Pgp activity induced by ATRA. These results show that RARalpha overexpression in leukemic cells could result in MDR.
Stromskaya
Tatjana P
TP
Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Centre of the Russian Academy of Medical Sciences, Kashirskoye sh 24, Moscow 115478, Russia. stromskaya@mail.ru
Rybalkina
Ekaterina Y
EY
Zabotina
Tatjana N
TN
Shishkin
Alexander A
AA
Stavrovskaya
Alla A
AA