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

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 bloodbrain 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.

Localization of Multidrug Resistance-Associated Proteins along the Blood-Testis Barrier in Rat, Macaque, and Human Testis

“…Within this family, P-gp (ABCB1), MRP1 (ABCC1), MRP4 (ABCC4), MRP5 (ABCC5), and MRP8 (ABCC11) mRNA expression has been found in rat Sertoli cells, and MRP2 and MRP3 were found to be expressed at low amounts (Bart et al, 2004;Augustine et al, 2005). Additionally, BCRP and P-gp have been localized in human testis to the peritubular myoid cells (Bart et al, 2004;Qian et al, 2013). The physiologic functions of MRP1, MRP4, and MRP5 are cytoprotective in many tissues and are known to efflux a wide variety of compounds (Klaassen and Aleksunes, 2010).…”

Inhibition of protein glycosylation reverses the MDR phenotype of cancer cell lines

“…Homo-dimerisation is necessary to create a functional BCRP efflux pump. BCRP is glycosylated at Asn596 in the third extracellular loop [8][9][10]. The molecular weight of unglycosylated BCRP is 60 kDa and it is increased to 70 kDa after glycosylation [11].…”

Malignant Tumours of the Central Nervous System in Kazakhstan - Incidence Trends from 2004-2011

“…Study has shown that brain tumors are more common in infertile women, as well as in women who have given birth to her first child late (after 30 years), and that they are often associated with breast cancer. However, these data are preliminary and require confirmation in well-designed epidemiological studies (Qian et al, 2013).…”