Expression and localisation of breast cancer resistance protein (BCRP) in human fetal membranes and decidua and the influence of labour at term

2008 ◽  
Vol 20 (2) ◽  
pp. 328 ◽  
Author(s):  
D. Yeboah ◽  
G. M. Kalabis ◽  
M. Sun ◽  
R. C. Ou ◽  
S. G. Matthews ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Blood Vessels ◽  
Stromal Cells ◽  
Breast Cancer Resistance Protein ◽  
Fetal Membranes ◽  
Apical Surface ◽  
Cancer Resistance ◽  
Chemotherapy Drugs ◽  
Wide Range ◽  
Resistance Protein

Breast cancer resistance protein (BCRP) is a multidrug resistant ABC transport protein (ABCG-2). It extrudes a wide range of substrates, including many chemotherapy drugs, steroids and folate. It is present in many cancers, as well as normal tissues, in particular barrier tissues such as the blood–brain barrier, the intestine, blood vessels and the human placenta. Human fetal membranes (amnion and chorion laeve) provide the barrier between the maternal uterine environment and the fetus. In the present study, we defined the expression and localisation of BCRP mRNA and protein in human fetal membranes (amnion and chorion) and attached decidua obtained before and following labour at term. BCRP protein and mRNA was expressed in all tissues examined and the levels of expression were not altered by labour. BCRP was localised to the amnion epithelial cells, chorion trophoblast cells and decidua stromal cells, as well as the endothelial cells of maternal blood vessels in the decidua, but was absent from mesenchymal cells. In the amnion epithelium, BCRP protein was localised to the apical surface, cytoplasm and membrane between cells. In the chorion trophoblast and decidua stromal cells, BCRP protein was localised to the plasma membrane. However, in the chorion trophoblast, BCRP protein was also highly expressed in the nucleus. The level of BCRP protein in the membranes was comparable to that in the placenta. These high levels raise the possibility that this transporter plays an important role in the physiological function of the tissues.

scholarly journals Cryptotanshinone Breaks ERα-dependent and -independent BCRP Dimerization to Reverse the Multidrug Resistance in Breast Cancer

2020 ◽  
Author(s):  
Wenting Ni ◽  
Hui Fan ◽  
Xiuqin Zheng ◽  
Fangming Xu ◽  
Yuanyuan Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Multidrug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Estrogen Therapy ◽  
Resonance Energy ◽  
Cancer Resistance ◽  
Microscopy Imaging ◽  
Chemotherapy Drugs ◽  
Resistance Protein

Abstract Background: Not only a long-term anti-estrogen therapy, but also estrogen receptor-negative breast cancer are generally prone to induce resistance, causing poor prognosis in clinic. Breast cancer resistance protein (BCRP) plays an important role in multidrug resistance. Here it is to elucidate the mechanism that a natural compound cryptotanshinone inhibits BCRP.Methods: HPLC was for analyzing the special compound concentration and molecular docking assay for the affinity of compound with protein. Non-reducing gradient gel electrophoresis and fluorescence resonance energy transfer (FRET) microscopy imaging were used to detect polymer and stain the membrane protein. Immunofluorescence staining, plasmids transfection, real-time PCR and western blot were also used.Results: Cryptotanshinone, an anti-estrogen compound was firstly found to inhibit breast cancer resistance protein (BCRP) membrane dimerization to attenuate its transport function. And this process is dependent on estrogen receptor α (ERα) in breast cancer. Furthermore, the resistant breast cancer cells with high BCRP expression are also sensitive to cryptotanshinone because it can bind to BCRP and significantly inhibit membrane dimer of BCRP although they are ERα-negative, suggesting that BCRP expression is essential to cryptotanshinone reversing the resistance; Meanwhile, the combination of cryptotanshinone and chemotherapy drugs could obviously enhance the chemotherapeutic effect. Conclusion: Cryptotanshinone is a novel natural BCRP inhibitor via blocking the formation of BCRP membrane dimer by an ERα-dependent and -independent way. Cryptotanshinone reverses resistance dependent on BCRP in breast cancer.

Expression of breast cancer resistance protein (BCRP/ABCG2) in human placenta throughout gestation and at term before and after labor

2006 ◽  
Vol 84 (12) ◽  
pp. 1251-1258 ◽  
Author(s):  
D. Yeboah ◽  
M. Sun ◽  
J. Kingdom ◽  
D. Baczyk ◽  
S.J. Lye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Blood Vessels ◽  
Human Placenta ◽  
Breast Cancer Resistance Protein ◽  
Fold Increase ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Cancer Resistance ◽  
Protein Levels ◽  
Resistance Protein

Breast cancer resistance protein, BCRP, is a multidrug resistance protein that is highly expressed in the human placenta. In cancer tissues, this protein actively extrudes a wide variety of chemically and structurally unrelated chemotherapeutic drugs and other compounds. Studies in mice have shown that in the absence of BCRP activity in the placenta, there is a 2-fold increase in the uptake in BCRP substrates into fetus. This suggests that in the placenta, BCRP extrudes compounds that would otherwise cross the syncytiotrophoblast cells into fetal circulation. The purpose of this study was to examine the expression and localization of BCRP in the human placenta throughout gestation. Tissues from 6–13, 16–19, 24–29, 32–35, and 38–41 weeks of gestation were used. Real time RT-PCR analysis demonstrated that the mRNA levels of BCRP in the placenta do not change significantly as gestation progressed. However, Western blot analysis revealed that the protein levels increased towards the end of gestation. We demonstrated that BCRP is localized to the syncytiotrophoblast of the placenta and in some fetal blood vessels within the placenta. Tissues from the early stages of pregnancy (6–13 weeks) showed fewer BCRP positive blood vessels than term tissues (38–41 weeks).

Cryptotanshinone Breaks ERα-dependent and -independent BCRP Dimerization to Reverse the Multidrug Resistance in Breast Cancer

2020 ◽  
Author(s):  
Wenting Ni ◽  
Hui Fan ◽  
Xiuqin Zheng ◽  
Fangming Xu ◽  
Yuanyuan Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Multidrug Resistance ◽  
Breast Cancer Resistance Protein ◽  
Estrogen Therapy ◽  
Resonance Energy ◽  
Cancer Resistance ◽  
Microscopy Imaging ◽  
Chemotherapy Drugs ◽  
Resistance Protein

Abstract Background Not only a long-term anti-estrogen therapy, but also estrogen receptor-negative breast cancer are generally prone to induce resistance, causing poor prognosis in clinic. Breast cancer resistance protein (BCRP) plays an important role in multidrug resistance. Here it is to elucidate the mechanism that a natural compound cryptotanshinone inhibits BCRP. Methods HPLC was for analyzing the special compound concentration and molecular docking assay for the affinity of compound with protein. Non-reducing gradient gel electrophoresis and fluorescence resonance energy transfer (FRET) microscopy imaging were used to detect polymer and stain the membrane protein. Immunofluorescence staining, plasmids transfection, real-time PCR and western blot were also used. Results Cryptotanshinone, an anti-estrogen compound was firstly found to inhibit breast cancer resistance protein (BCRP) membrane dimerization to attenuate its transport function. And this process is dependent on estrogen receptor α (ERα) in breast cancer. Furthermore, the resistant breast cancer cells with high BCRP expression are also sensitive to cryptotanshinone because it can bind to BCRP and significantly inhibit membrane dimer of BCRP although they are ERα-negative, suggesting that BCRP expression is essential to cryptotanshinone reversing the resistance; Meanwhile, the combination of cryptotanshinone and chemotherapy drugs could obviously enhance the chemotherapeutic effect. Conclusion Cryptotanshinone is a novel natural BCRP inhibitor via blocking the formation of BCRP membrane dimer by an ERα-dependent and -independent way. Cryptotanshinone reverses resistance dependent on BCRP in breast cancer.

Breast Cancer Resistance Protein: A Potential Therapeutic Target for Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Sonali Mehendale-Munj
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Resistance Protein ◽  
Protein A ◽  
The Body ◽  
Cancer Therapies ◽  
Cancer Resistance ◽  
Lung Cancers ◽  
Resistance Protein ◽  
Atp Regulation ◽  
Treatment Procedures

: Breast Cancer Resistance Protein (BCRP) is an efflux transporter responsible for causing multidrug re-sistance(MDR). It is known to expel many potent antineoplastic drugs, owing to its efflux function. Efflux of chemothera-peutics because of BCRP develops resistance to manydrugs, leading to failure in cancer treatment. BCRP plays an important role in physiology by protecting the organism from xenobiotics and other toxins. It is a half-transporter affiliated to theATP-binding cassette (ABC) superfamily of transporters, encoded by the gene ABCG2 and functions in response to adenosine triphosphate (ATP). Regulation of BCRP expression is critically controlled at molecular levels which help in maintaining the balance of xenobiotics and nutrients inside the body. Expression of BCRP can be found in brain, liver, lung cancers and acute myeloid leukemia (AML). Moreover, it is also expressed at high levels in stem cells and many cell lines. This frequent expression of BCRP has an impact on the treatment procedures and if not scrutinized may lead to failure of many cancer therapies.

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