Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling
Clinically, breast cancer is generally classified into estrogen receptor-positive (ER+) or estrogen receptor-negative (ER-) subtypes. The phytoestrogen calycosin has been shown to inhibit the proliferation of ER+ cells, which may be mediated by a feedback loop that involves miR-375, RAS dexamethason...
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Published in | Journal of experimental & clinical cancer research Vol. 36; no. 1; p. 153 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BioMed Central Ltd
02.11.2017
BioMed Central BMC |
Subjects | |
Online Access | Get full text |
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Summary: | Clinically, breast cancer is generally classified into estrogen receptor-positive (ER+) or estrogen receptor-negative (ER-) subtypes. The phytoestrogen calycosin has been shown to inhibit the proliferation of ER+ cells, which may be mediated by a feedback loop that involves miR-375, RAS dexamethasone-induced 1 (RASD1), and ERα. However, how calycosin acts on ER- breast cancer cells remains unclear.
Here, we show that calycosin inhibited the proliferation of both ER- (MDA-MB-468 and SKBR3) and ER+ breast cancer cells (MCF-7 and T47D) and that these inhibitory effects were associated with the up-regulation of the long non-coding RNA (lncRNA) WDR7-7. For the first time, we demonstrate that the expression of WDR7-7 is reduced in breast cancer cell lines and that the overexpression of WDR7-7 inhibits growth through a mechanism that involves G-protein coupled estrogen receptor 30 (GPR30). Meanwhile, we show that calycosin stimulated the WDR7-7-GPR30 signaling pathway in MCF-7, T47D, MDA-MB-468, and SKBR3 breast cancer cells. In contrast, in MCF10A and GPR30-deficient MDA-MB-231 cells, due to a lack of WDR7-7-GPR30 for activation, calycosin failed to inhibit cell growth. Additionally, in all four GPR30-positive breast cancer lines, calycosin decreased the phosphorylation levels of SRC, EGFR, ERK1/2 and Akt, but the inhibition of WDR7-7 blocked these changes and increased proliferation. In mice bearing MCF-7 or SKBR3 xenografts, tumor growth was inhibited by calycosin, and changes in expression the levels of WDR7-7 and GPR30 in tumor tissues were similar to those in cultured MCF-7 and SKBR3 cells.
These results suggest the possibility that calycosin inhibited the proliferation of breast cancer cells, at least partially, through WDR7-7-GPR30 signaling, which may explain why calycosin can exert inhibitory effects on ER- breast cancer. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1756-9966 0392-9078 1756-9966 |
DOI: | 10.1186/s13046-017-0625-y |