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https://hdl.handle.net/2440/9699
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Type: | Journal article |
Title: | Sphingosine kinase transmits estrogen signaling in human breast cancer cells |
Author: | Sukocheva, O. Wang, L. Albanese, N. Pitson, S. Vadas, M. Xia, P. |
Citation: | Molecular Endocrinology, 2003; 17(10):2002-2012 |
Publisher: | Endocrine Soc |
Issue Date: | 2003 |
ISSN: | 0888-8809 1944-9917 |
Abstract: | Current understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report that treatment with 17beta-estradiol (E2) activates a novel signaling pathway via activation of sphingosine kinase (SphK) in MCF-7 breast cancer cells. We found that E2 has dual actions to stimulate SphK activity, i.e. a rapid and transient activation mediated by putative membrane G protein-coupled estrogen receptors (ER) and a delayed but prolonged activation relying on the transcriptional activity of ER. The E2-induced SphK activity consequently activates downstream signal cascades including intracellular Ca2+ mobilization and Erk1/2 activation. Enforced expression of human SphK type 1 gene in MCF-7 cells resulted in increases in SphK activity and cell growth. Moreover, the E2-dependent mitogenesis were highly promoted by SphK overexpression as determined by colony growth in soft agar and solid focus formation. In contrast, expression of SphKG82D, a dominant-negative mutant SphK, profoundly inhibited the E2-mediated Ca2+ mobilization, Erk1/2 activity and neoplastic cell growth. Thus, our data suggest that SphK activation is an important cytoplasmic signaling to transduce estrogen-dependent mitogenic and carcinogenic action in human breast cancer cells. |
Keywords: | Cell Line, Tumor Humans Breast Neoplasms Calcium Estradiol Estrogen Receptor Modulators Estrogen Antagonists Phosphotransferases (Alcohol Group Acceptor) Mitogen-Activated Protein Kinases Receptors, Estrogen Antineoplastic Agents, Hormonal Estrogens Transfection Signal Transduction Cell Division Gene Expression Regulation Enzyme Activation Protein Binding Female |
DOI: | 10.1210/me.2003-0119 |
Published version: | http://mend.endojournals.org/cgi/reprint/17/10/2002.pdf |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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