@article {Kawabata:February 2001:0006-291X:1216, author = "Kawabata S.", author = "Oka M.", author = "Shiozawa K.", author = "Tsukamoto K.", author = "Nakatomi K.", author = "Soda H.", author = "Fukuda M.", author = "Ikegami Y.", author = "Sugahara K.", author = "Yamada Y.", author = "Kamihira S.", author = "Doyle L.A.", author = "Ross D.D.", author = "Kohno S.", title = "Breast Cancer Resistance Protein Directly Confers SN-38 Resistance of Lung Cancer Cells", journal = "Biochemical and Biophysical Research Communications", volume = "280", year = "February 2001", abstract = "

Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone. BCRP-overexpressing cells show cross-resistance to camptothecin derivatives such as irinotecan, SN-38 (the active metabolite of irinotecan), and topotecan. To test whether BCRP confers SN-38 resistance, we selected two SN-38 resistant sublines from PC-6 human small-cell lung cancer cells by SN-38, and then characterized these cells. Compared to PC-6 cells, the resistant sublines PC-6/SN2-5 and PC-6/SN2-5H were approximately 18- and 34-fold resistant, respectively. The intracellular SN-38 accumulation was reduced in the sublines, and BCRP mRNA was overexpressed in proportion to the degree of SN-38 resistance. These findings suggest that BCRP confers SN-38 resistance in the sublines. To confirm this hypothesis, PC-6/SN2-5 cells were transfected with antisense oligonucleotides complementary to portions of BCRP mRNA. The antisense oligonucleotides significantly suppressed BCRP mRNA expression, and enhanced SN-38 sensitivity in the subline. These data indicate that BCRP is directly involved with SN-38 resistance, by efflux transport of SN-38. Copyright 2001 Academic Press.

", pages = "1216-1223(8)", url = "http://www.ingentaconnect.com/content/ap/rc/2001/00000280/00000005/art04267" }