2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative Cells
2-Methoxyestradiol (2-ME2) was reported to elicit both stimulation and inhibition of tumor angiogenesis and growth depending on the dosage used. However, the mechanism(s) of the biphasic action of 2-ME2 has been elusive. Here we describe a regulatory role of vascular endothelial growth factor-A (VE...
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doaj-9520fc4da0e845288b872ecbcce927382020-11-24T22:55:06ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022003-09-015541742610.1016/S1476-5586(03)80044-12-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative CellsSamarendra N. Banerjee0Krishanu Sengupta1Snigdha Banerjee2Neela K. Saxena3Sushanta K. Banerjee4Cancer Research Unit, V.A. Medical Center, Kansas City, KS, USACancer Research Unit, V.A. Medical Center, Kansas City, KS, USACancer Research Unit, V.A. Medical Center, Kansas City, KS, USACancer Research Unit, V.A. Medical Center, Kansas City, KS, USACancer Research Unit, V.A. Medical Center, Kansas City, KS, USA 2-Methoxyestradiol (2-ME2) was reported to elicit both stimulation and inhibition of tumor angiogenesis and growth depending on the dosage used. However, the mechanism(s) of the biphasic action of 2-ME2 has been elusive. Here we describe a regulatory role of vascular endothelial growth factor-A (VEGF-A) in the biphasic effects on estrogen receptor (ER)+ GH3 rat pituitary tumor cells and MCF-7 human breast tumor cells depending on the dosage of 2-ME2 used. We observed that acute exposure to 2-ME2, irrespective of dosage, did not alter cellular proliferation, but enhanced the VEGF-A mRNA level. As the treatment duration increased, biphasic effect was elicited. A concentration of 1 μM 2-ME2 increased both cell proliferation and VEGF-A levels in these cells, whereas higher doses exhibited reversed impact. A low dose of 2-ME2 also increased the VEGF-A mRNA expression in ER-α-transfected human mammary epithelial cells (HMECs). The effect was reversed in ER- cells. The enhanced expression of VEGF-A mRNA could be blocked by the pure estrogen antagonist, ICI 182,780, reveal that the upregulation of VEGF-A expression by 2-ME2 is mediated through ER-α. Furthermore, the biphasic effect of 2-ME2 on cell proliferation can be modulated by administrating VEGF-A antibodies or VEGF-A proteins. Studies also demonstrate that the VEGF-A protein, induced by 2-ME2, is functionally active and upregulates the proliferation of adjacent endothelial cells. http://www.sciencedirect.com/science/article/pii/S14765586038004412-methoxyestadiolVEGFER-alphahuman mammary epithelial cellstransfection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Samarendra N. Banerjee Krishanu Sengupta Snigdha Banerjee Neela K. Saxena Sushanta K. Banerjee |
spellingShingle |
Samarendra N. Banerjee Krishanu Sengupta Snigdha Banerjee Neela K. Saxena Sushanta K. Banerjee 2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative Cells Neoplasia: An International Journal for Oncology Research 2-methoxyestadiol VEGF ER-alpha human mammary epithelial cells transfection |
author_facet |
Samarendra N. Banerjee Krishanu Sengupta Snigdha Banerjee Neela K. Saxena Sushanta K. Banerjee |
author_sort |
Samarendra N. Banerjee |
title |
2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative Cells |
title_short |
2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative Cells |
title_full |
2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative Cells |
title_fullStr |
2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative Cells |
title_full_unstemmed |
2-Methoxyestradiol Exhibits a Biphasic Effect on VEGF-A in Tumor Cells and Upregulation Is Mediated Through ER-α: A Possible Signaling Pathway Associated with the Impact of 2-ME2 on Proliferative Cells |
title_sort |
2-methoxyestradiol exhibits a biphasic effect on vegf-a in tumor cells and upregulation is mediated through er-α: a possible signaling pathway associated with the impact of 2-me2 on proliferative cells |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2003-09-01 |
description |
2-Methoxyestradiol (2-ME2) was reported to elicit both stimulation and inhibition of tumor angiogenesis and growth depending on the dosage used. However, the mechanism(s) of the biphasic action of 2-ME2 has been elusive. Here we describe a regulatory role of vascular endothelial growth factor-A (VEGF-A) in the biphasic effects on estrogen receptor (ER)+ GH3 rat pituitary tumor cells and MCF-7 human breast tumor cells depending on the dosage of 2-ME2 used. We observed that acute exposure to 2-ME2, irrespective of dosage, did not alter cellular proliferation, but enhanced the VEGF-A mRNA level. As the treatment duration increased, biphasic effect was elicited. A concentration of 1 μM 2-ME2 increased both cell proliferation and VEGF-A levels in these cells, whereas higher doses exhibited reversed impact. A low dose of 2-ME2 also increased the VEGF-A mRNA expression in ER-α-transfected human mammary epithelial cells (HMECs). The effect was reversed in ER- cells. The enhanced expression of VEGF-A mRNA could be blocked by the pure estrogen antagonist, ICI 182,780, reveal that the upregulation of VEGF-A expression by 2-ME2 is mediated through ER-α. Furthermore, the biphasic effect of 2-ME2 on cell proliferation can be modulated by administrating VEGF-A antibodies or VEGF-A proteins. Studies also demonstrate that the VEGF-A protein, induced by 2-ME2, is functionally active and upregulates the proliferation of adjacent endothelial cells.
|
topic |
2-methoxyestadiol VEGF ER-alpha human mammary epithelial cells transfection |
url |
http://www.sciencedirect.com/science/article/pii/S1476558603800441 |
work_keys_str_mv |
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