J Breast Cancer.  2011 Mar;14(1):20-27. 10.4048/jbc.2011.14.1.20.

Role of Estrogen Receptor-alpha in the Regulation of Claudin-6 Expression in Breast Cancer Cells

• Yafang L
• Qiong W
• Yue R
• Xiaoming X
• Lina Y
• Mingzi Z
• Ting Z
• Yulin L
• Chengshi Q

• KMID: 2175638
• DOI: http://doi.org/10.4048/jbc.2011.14.1.20

Abstract

PURPOSE
In our previous studies we showed that upregulating claudin-6 (CLDN6) expression may contribute to preventing breast cancer, and that 17beta-estradiol induces a concentration- and time-related effect on CLDN6 mRNA and protein expression in MCF-7 cells. However, the mechanisms of 17beta-estradiol regulation of CLDN6 are still unclear. We determined the role of estrogen receptors in the regulation of CLDN6 expression in human breast cancer tissues and a cell line.
METHODS
CLDN6, estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) expression in breast cancer tissues were examined using immunohistochemistry. The human breast cancer cell line, MCF-7, which expresses ERalpha but not ERbeta was used. CLDN6 and ERalpha expression were measured by reverse transcriptase-PCR, Western blotting and immunofluorescent staining. Treatments with propyl pyrazole triol (PPT) and ICI 182, 780 (ICI) were performed.
RESULTS
The results revealed that CLDN6 expression was related to ERalpha in breast cancer tissues (p=0.033). PPT, an ERalpha-selective ligand, upregulated CLDN6 expression at 10-5 mol/L after 24 hours. The effect of PPT on regulating CLDN6 expression in MCF-7 cells was blocked by ICI.
CONCLUSION
These findings suggest that Eralpha reulates CLDN6 expression in breast cancer tissues and that 17beta-estradiol induces CLDN6 expression through an ERalpha pathway in MCF-7 cells.

Keyword

Breast carcinoma; Claudins; Estrogen; Estrogen receptor alpha; Tight junctions

MeSH Terms

Blotting, Western
Breast
Breast Neoplasms
Cell Line
Claudins
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens
Humans
Immunohistochemistry
MCF-7 Cells
Pyrazoles
Receptors, Estrogen
RNA, Messenger
Tight Junctions
Claudins
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens
Pyrazoles
RNA, Messenger
Receptors, Estrogen