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Cell Growth & Differentiation, Vol 5, Issue 10 1145-1152, Copyright © 1994 by American Association of Cancer Research


ARTICLES

Enhanced expression by the brain matrix of P-glycoprotein in brain capillary endothelial cells

T Tatsuta, M Naito, K Mikami and T Tsuruo
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.

P-glycoprotein (PGP), an active efflux pump of antitumor agents in multidrug-resistant tumor cells, exists in brain capillary endothelium and could be functionally involved in the blood-brain barrier. To study the regulatory mechanism of PGP expression in brain capillary endothelium, various mouse tissue matrices were tested for their abilities to enhance the expression of PGP in mouse brain capillary endothelial cells (MBEC), which express relatively small amounts of PGP. Of the four tissue matrices we examined, PGP expression in MBEC cultured on the brain matrix increased 2.0-fold. The PGP-inducing activity was similarly detected in bovine brain matrix, and the activity was enriched in the fraction of pl 9.0 by isoelectric focusing. The fraction, named PIC-fraction (PGP-inducing component), increased the PGP expression in MBEC 3.5-fold. By Northern blot analysis, a 3.3-fold enhancement of mdr gene expression was observed in MBEC cultured on the PIC-fraction. The PGP-inducing activity of the PIC-fraction was reduced by the treatment with trypsin but not with collagenase, suggesting that a proteinaceous factor distinct from type I collagen might be responsible for the PGP-inducing activity of PIC-fraction. Although the PIC-fraction increased the PGP expression in other mouse brain capillary endothelial cells, the PIC-fraction did not increase PGP expression in mouse aortic endothelial cells and KB carcinoma cell lines expressing various amounts of PGP. These observations suggest that PGP expression in brain capillary endothelium is specifically regulated by a tissue-specific factor in the brain matrix.


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T. Miyama, H. Takanaga, H. Matsuo, K. Yamano, K. Yamamoto, T. Iga, M. Naito, T. Tsuruo, H. Ishizuka, Y. Kawahara, et al.
P-Glycoprotein-Mediated Transport of Itraconazole across the Blood-Brain Barrier
Antimicrob. Agents Chemother., July 1, 1998; 42(7): 1738 - 1744.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1994 by the American Association of Cancer Research.