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J Exp Clin Cancer Res. 2017 Nov 2;36(1):153. doi: 10.1186/s13046-017-0625-y.

Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling.

Author information

1
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, 541004, China.
2
Department of Physiology, Guilin Medical University, Guilin, Guangxi, China.
3
Department of Breast and Thyroid Surgery, First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
4
Department of Pathology and Physiopathology, Guilin Medical University, Guilin, Guangxi, China.
5
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, 541004, China. chjian80726@163.com.

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Breast cancer; Calycosin; GPR30; Long non-coding RNA; WDR7-7

PMID:
29096683
PMCID:
PMC5667511
DOI:
10.1186/s13046-017-0625-y
[Indexed for MEDLINE]
Free PMC Article

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