scholarly journals SLCO and SLC22 Solute Carriers: Establishing Differential Expression Patterns in Human Breast Cancer Cell Lines and Tumour Samples

Author(s):  
Rachel Sutherland ◽  
Annette Meeson ◽  
Simon Lowes

Abstract Background: The uptake of nutrients essential for cell growth and survival is facilitated by solute carrier (SLC) transporters. The SLCO and SLC22 subfamilies mediate the uptake of substrates relevant to breast cancer (BC), including steroid hormones and anticancer drugs, and accumulating evidence suggests that altered expression of these transporters may affect BC pathogenesis by influencing cell proliferation and anticancer drug resistance. Methods: The differential expression of 11 SLCO and 14 SLC22 transporters was investigated using semi-quantitative and quantitative PCR in MCF-7 and MDA-MB-231 BC cell lines and in human BC tissue samples. Results: 8 SLCO and 10 SLC22 transporters were expressed in at least one cell line. Of these SLCO1B1, SLCO1B3, SLCO3A1, SLC22A1, SLC22A3, SLC22A4 and SLC22A16 showed higher expression in MDA-MB-231 than MCF-7 cells. Conversely, SLCO2A1, SLCO4A1, SLCO4C1, SLCO5A1, SLC22A5 showed higher expression in MCF-7 than MDA-MB-231 cells. In four human breast cancer samples, there was variable expression of the 25 SLC transporters, however, 11 SLCO and 9 SLC22 transporters were detected in at least one sample. Conclusion: BC cells express a variety of SLCs capable of transporting a range of steroid hormones and clinically relevant anticancer drugs, which could implicate them in BC pathogenesis and anti-cancer drug resistance.

2005 ◽  
Vol 12 (3) ◽  
pp. 599-614 ◽  
Author(s):  
T Frogne ◽  
J S Jepsen ◽  
S S Larsen ◽  
C K Fog ◽  
B L Brockdorff ◽  
...  

Development of acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. The IGF system plays a profound role in many cancer types, including breast cancer. Thus, overexpression and/or constitutive activation of the IGF-I receptor (IGF-IR) or different components of the IGF-IR signaling pathway have been reported to render breast cancer cells less estrogen dependent and capable of sustaining cell proliferation in the presence of antiestrogens. In this study, growth of the antiestrogen-sensitive human breast cancer cell line MCF-7 was inhibited by treatment with IGF-IR-neutralizing antibodies. In contrast, IGF-IR-neutralizing antibodies had no effect on growth of two different antiestrogen-resistant MCF-7 sublines. A panel of antiestrogen-resistant cell lines was investigated for expression of IGF-IR and either undetectable or severely reduced IGF-IR levels were observed. No increase in insulin receptor substrate 1 (IRS-1) or total PKB/Akt (Akt) was detected in the resistant cell lines. However, a significant increase in phosphorylated Akt (pAkt) was found in four of six antiestrogen-resistant cell lines. Overexpression of pAkt was associated with increased Akt kinase activity in both a tamoxifen- and an ICI 182,780-resistant cell line. Inhibition of Akt phosphorylation by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin or the Akt inhibitor SH-6 (structurally modified phosphatidyl inositol ether liquid analog PIA 6) resulted in a more pronounced growth inhibitory effect on the antiestrogen-resistant cells compared with the parental cells, suggesting that signaling via Akt is required for antiestrogen-resistant cell growth in at least a subset of our antiestrogen-resistant cell lines. PTEN expression and activity was not decreased in cell lines overexpressing pAkt. Our data demonstrate that Akt is a target for treatment of antiestrogen-resistant breast cancer cell lines and we suggest that antiestrogen-resistant breast cancer patients may benefit from treatment targeted to inhibit Akt signaling.


Author(s):  
Nadjiba Zegheb ◽  
Cherifa Boubekri ◽  
Touhami Lanez ◽  
Elhafnaoui Lanez ◽  
Tuba Tüylü Küçükkılınç ◽  
...  

Background: Since the binding of estradiol to its receptor promotes breast cancer cell proliferation (in the ER+ tumours), many molecules targeting this protein have been synthesized to counteract the estradiol action. Ferrocene derivatives have proved their efficiency against hormone-dependent breast cancer cells (MCF-7). Objective: In this study, we aimed to find new ferrocene derivatives having pharmacochemistry properties as potential drugs against human breast cancer cells. Methods: A series of 29 N-ferrocenylmethylaniline derivatives A0-A28 were synthesised, and their anti-proliferative activity against both hormone-dependent (MCF-7) and independent (MDA-MB 231) human breast cancer cell lines were performed using the MTT test. Molecular docking and drug-likeness prediction were also performed for the five most active derivatives towards MCF-7. A QSAR model was also developed for the perdition of the anti-proliferative activity against MCF-7 cell lines using molecular descriptors and MLR analysis. Results: All studied derivatives demonstrated better cytotoxicity against MCF-7 compared to the MDA-MB-231 cell lines, and compounds A2, A9, A14, A17, and A27 were the most potent ones; however, but still less active than the standard anti-cancer drug crizotinib. The QSAR study revealed good predictive ability as shown by R2cv = 0.848. Conclusion: In vitro and in silico results indicated that derivatives A2, A9, A14, A17, and A27 possess the highest anti-proliferative activity, t. These results can be used to design more potent N-ferrocenylmethylaniline derivatives as anti-proliferative agents.


2010 ◽  
Vol 24 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Leila Büttner Mostaço-Guidolin ◽  
Luciana Sayuri Murakami ◽  
Marina Ribeiro Batistuti ◽  
Auro Nomizo ◽  
Luciano Bachmann

The present study was designed to identify and compare the infrared absorption spectra of two human breast cancer cell lines: MCF-7 (estrogen receptor expressed, ER+) and SKBr3 (estrogen receptor non-expressed, ER–). Comparison between SKBr3 and MCF-7 cells revealed differences in the following absorption band areas: 1087 cm–1(DNA), 1397 cm–1(CH3), 1543 cm–1(amide II), 1651 cm–1(amide I), 2924 cm–1(fatty acids). Additionally, peak shifts were observed at 1122 cm–1(RNA), 1397 cm–1(CH3), 1651 cm–1(amide I), 2851 cm–1(fatty acids) and 2962 cm–1(fatty acids). An analysis of the ratio between band areas was conducted, in order to obtain an index that could effectively distinguish between these two cell lines. The following ratios were found: 1650 cm–1/1540 cm–1, 1650 cm–1/1740 cm–1, 1650 cm–1/1084 cm–1and 1120 cm–1/1084 cm–1. This work demonstrates that it is possible to distinguish between MCF-7 and SKBr3 cells through differences in their FTIR spectra. This work enables distinction between two cell lines from the same breast cancer.


Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3218 ◽  
Author(s):  
Fu Peng ◽  
Huan Zhu ◽  
Chun-Wang Meng ◽  
Yan-Rui Ren ◽  
Ou Dai ◽  
...  

The rattans of Spatholobus suberectus Dunn are a traditional Chinese medicine activating blood circulation and removing stasis. They have often been used for the traditional Chinese medicinal treatment of breast cancer in modern China. In this study, four novel isoflavanes (1–3 and 5) and four known analogues (4 and 6–8) were isolated from an ethanolic extract of the rattans of S. suberectus. Their structures were elucidated by extensive spectroscopic analyses and electronic circular dichroism studies. MCF-7 and MDA-MB-231 human breast cancer cell lines were used to evaluate the cytotoxic effects of the isolates. Interestingly, compounds 1 and 2 only inhibited the proliferation of MCF-7 cells, while compound 6 showed a selective cytotoxicity against MDA-MB-231 cells. However, compound 4 had significant cytotoxicity against both MCF-7 and MDA-MB-231 cell lines.


2002 ◽  
Vol 34 (4) ◽  
pp. 165-171 ◽  
Author(s):  
Kate M. Suchanek ◽  
Fiona J. May ◽  
Jodie A. Robinson ◽  
Won Jae Lee ◽  
Nicola A. Holman ◽  
...  

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