Effect of Estradiol on xc- in Human Breast Cancer Cells

Effect of Estradiol on xc- in Human Breast Cancer Cells

Bibliographic Details
Main Author: Ellis, Jillian L.
Language:English
Published: University of Cincinnati / OhioLINK 2012
Subjects:
Pharmaceuticals
xc- transporter
sulfasalazine
breast cancer
cystine
glutamate
glutathione
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1352488961
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin13524889612021-08-03T05:20:30Z Effect of Estradiol on xc- in Human Breast Cancer Cells Ellis, Jillian L. Pharmaceuticals xc- transporter sulfasalazine breast cancer cystine glutamate glutathione <p></p><p>Breast cancer is the most common cancer among women worldwide with hundreds of thousands of new cases diagnosed each year in the United States alone. The discovery of receptors has improved the specificity of diagnoses, enabling development of receptor specific treatments. The discovery of the estrogen receptor (ER), in particular, has led to the development of antiestrogens such as tamoxifen for the treatment of breast cancer. Despite the vast improvement antiestrogens have made, there is still a growing need to find new therapeutic targets to compensate for resistance that is developing to both the antiestrogens and chemotherapy. One potential target discovered in the 1980s is the xc- system, a cystine/glutamate antiporter. As knowledge about this system has increased, it has been found to have many characteristics of a possible target for cancer treatment. This transporter can be aberrantly expressed in many cancers including breast cancer. It is crucial in these cells for the uptake of cystine, which is important for two reasons. First, cystine and the reduced form cysteine are necessary for normal protein formation. Secondly, cysteine inside the cell is the rate limiting precursor for glutathione synthesis and therefore regulates cellular defense against oxidative stress. The drug sulfasalazine (SASP) has been shown to specifically inhibit this system leading to cell stasis and glutathione depletion. Using the ER positive human breast cancer cell line MCF-7, the xc- specific subunit, xCT, mRNA and protein expression were found to decrease following treatment with estradiol. Additionally, estradiol was found to decrease the doubling time of these cells, while sulfasalazine increased the doubling time. Interestingly, it was found that estradiol decreased the doubling time of MCF-7 cells when compared to cells treated with the same concentration of SASP but without estradiol. Similarly, estradiol seems to cause an increase in the concentration of SASP necessary to cause a significant increase in doubling time. We conclude that estradiol does have a regulatory effect on the xc- system. Estradiol also affects a pathway that overwhelms the inhibitory effect of SASP. Finally, we propose that this downregulation of xCT may be due to nongenomic action of the estradiol bound membrane associated ER and activation of protein kinase signaling cascades.</p> 2012 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1352488961 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1352488961 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Pharmaceuticals
xc- transporter
sulfasalazine
breast cancer
cystine
glutamate
glutathione
spellingShingle Pharmaceuticals
xc- transporter
sulfasalazine
breast cancer
cystine
glutamate
glutathione
Ellis, Jillian L.
Effect of Estradiol on xc- in Human Breast Cancer Cells
author Ellis, Jillian L.
author_facet Ellis, Jillian L.
author_sort Ellis, Jillian L.
title Effect of Estradiol on xc- in Human Breast Cancer Cells
title_short Effect of Estradiol on xc- in Human Breast Cancer Cells
title_full Effect of Estradiol on xc- in Human Breast Cancer Cells
title_fullStr Effect of Estradiol on xc- in Human Breast Cancer Cells
title_full_unstemmed Effect of Estradiol on xc- in Human Breast Cancer Cells
title_sort effect of estradiol on xc- in human breast cancer cells
publisher University of Cincinnati / OhioLINK
publishDate 2012
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1352488961
work_keys_str_mv AT ellisjillianl effectofestradiolonxcinhumanbreastcancercells
_version_ 1719418886083837952

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