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Abstract

Volume 15, Issue 4 (July 2013) 15, 455–460; 10.1038/aja.2013.24

Breast cancer resistance protein (Bcrp) and the testis—an unexpected turn of events

Xiaojing Qian1,2, Yan-Ho Cheng3, Dolores D Mruk1 and C Yan Cheng1

1 The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065, USA
2 Department of Anatomy, Histology and Embryology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
3 Richmond University Medical Center, Staten Island, NY 10301, USA

Correspondence: Dr CY Cheng, (Y-Cheng@popcbr.rockefeller.edu)

Received 19 November 2012; Revised 6 February 2013; Accepted 6 March 2013

Abstract

Breast cancer resistance protein (Bcrp) is an ATP-dependent efflux drug transporter. It has a diverse spectrum of hydrophilic and hydrophobic substrates ranging from anticancer, antiviral and antihypertensive drugs, to organic anions, antibiotics, phytoestrogens (e.g., genistein, daidzein, coumestrol), xenoestrogens and steroids (e.g., dehydroepiandrosterone sulfate). Bcrp is an integral membrane protein in cancer and normal cells within multiple organs (e.g., brain, placenta, intestine and testis) that maintains cellular homeostasis by extruding drugs and harmful substances from the inside of cells. In the brain, Bcrp is a major component of the blood–brain barrier located on endothelial cells near tight junctions (TJs). However, Bcrp is absent at the Sertoli cell blood–testis barrier (BTB); instead, it is localized almost exclusively to the endothelial TJ in microvessels in the interstitium and the peritubular myoid cells in the tunica propria. Recent studies have shown that Bcrp is also expressed stage specifically and spatiotemporally by Sertoli and germ cells in the seminiferous epithelium of rat testes, limited only to a testis-specific cell adhesion ultrastructure known as the apical ectoplasmic specialisation (ES) in stage VI–early VIII tubules. These findings suggest that Bcrp is equipped by late spermatids and Sertoli cells to protect late-stage spermatids completing spermiogenesis. Furthermore, Bcrp was found to be associated with F (filamentous)-actin and several actin regulatory proteins at the apical ES and might be involved in the organisation of actin filaments at the apical ES in stage VII–VIII tubules. These findings will be carefully evaluated in this brief review.

Keywords:actin filaments; breast cancer resistant protein; ectoplasmic specialisation; effux drug transporter; germ cells; Sertoli cells; spermatids; spermatogenesis; spermiogenesis; testis

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.