-transparent.png){kind=logo}
We provide evidence that the expression of the human MRP/GS-X pump encoded by the MRP (multidrug resistance associated protein) gene is induced by cisplatin in human leukemia HL-60/R-CP (cisplatin-resistant) cells and modulates cell growth inhibition by delta(7)-prostaglandin A1 (PGA1) methyl ester. The MRP mRNA level in HL-60/R-CP cells increased remarkably after a 24-h incubation with 20 microM cisplatin; interestingly, however, no amplification of the MRP gene was detected. In cisplatin-sensitive HL-60 cells, which express the MRP/GS-X pump at low levels, c-myc expression was substantially suppressed by delta(7)-PGA1 methyl ester and the cell cycle was arrested in G1 phase. By contrast, in HL-60/R-CP cells overexpressing the MRP/GS-X pump, c-myc expression and cell proliferation were much less affected by delta(7)-PGA1 methyl ester. This suggests that induction of the MRP/GS-X pump may confer on cancer cells resistance to anticancer prostaglandins and that the resistance mechanism may involve the increased efflux of PG-glutathione conjugates, as active intermediates, from the cells via the MRP/GS-X pump.
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
April 1996,
Journal of the National Cancer Institute,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
October 2001,
Biochemical pharmacology,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
January 1997,
Advances in experimental medicine and biology,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
December 2001,
Journal of bioenergetics and biomembranes,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
September 1998,
Cytotechnology,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
August 1996,
Cancer research,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
January 2002,
Cancer treatment and research,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
June 1998,
Biochemical and biophysical research communications,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
September 1998,
Biochemistry and molecular biology international,
K Akimaru, and
M T Kuo, and
K Furuta, and
M Suzuki, and
R Noyori, and
T Ishikawa
March 1998,
Biochemical pharmacology,
