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Overexpression of estrogen receptor-α gene suppresses gap junctional intercellular communication in endometrial carcinoma cells

Oncogene volume 23, pages 1109–1116 (2004)Cite this article

Abstract

Stimulation of the endometrium by estrogens without the differentiating effect of progestins is the primary etiological factor associated with the development of endometrial hyperplasia and adenocarcinoma. However, the correlation between sex steroids and gap junctional intercellular communication (GJIC), which is considered to play an important role in the control of cell growth and differentiation, is not well known in endometrial carcinoma. In this study, we focused on the influence of estrogen and its receptor in connexin (Cx) expression and GJIC in endometrial carcinoma cells, established stable clone IK-ER1 overexpressing ER-α to transfect the expression vector and analysed them in various hormonal conditions. The growth of IK-ER1 was accelerated by 17β-estradiol and the acceleration of the 5-bromo-25-deoxyuridine labeling index was observed. GJIC was assayed by scoring the number of dye-coupled cells after microinjecton of single cells with Lucifer-Yellow, and subcellular localization of Cx26 and Cx32 was analysed by immunocytochemistry. In the presence of estradiol, dye-coupled cells of IK-ER1 were significantly reduced compared to those without estradiol and the reduction was completely inhibited by adding ICI182.780, a pure antiestrogen substrate. Cxs were detected as only small spots by immunocytochemistry, and Western blotting showed that the expression was decreased. These results suggest that activation of ER-α by estrogen results in tumor progression by stimulating cell growth and suppressing GJIC via suppression of the expression of Cxs in endometrial carcinogenesis.

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Abbreviations

GJIC:

gap junctional intercellular

ER:

estrogen receptor

PR:

progesterone receptor

E2:

17β-estradiol

Cx:

connexin

BrdU:

5-bromo-2′-deoxyuridine

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Acknowledgements

We are grateful to Dr P Chambon (Laboratoire de Génétique Moléculaire des Eucarytes du CNRS, Unité 184 de Biologie Moléculaire et de Génié Génétique de l'INSERM Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France) for the generous gift of a vector expressing hER (HEGO), and Dr M Nishida (Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Japan) for the gift of Ishikawa cell. We thank Mr M Kim Barrymore for editing the manuscript. Part of this work was supported by grants for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan: Contract Grant Numbers: 09470363, 09771289, 13214106, 14026053 and 14571575.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Sapporo Medical University, School of Medicine, S-1, W-16, Chuo-ku, Sapporo, 060-8543, Japan

    Tsuyoshi Saito, Ryoichi Tanaka, Koya Wataba & Ryuichi Kudo

  2. School of Science and Technology, Kwansei Gakuin University, 2-1, Gakuen, Sandai, 669-1337, Japan

    Hiroshi Yamasaki

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  1. Tsuyoshi Saito
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Correspondence to Tsuyoshi Saito.

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Saito, T., Tanaka, R., Wataba, K. et al. Overexpression of estrogen receptor-α gene suppresses gap junctional intercellular communication in endometrial carcinoma cells. Oncogene 23, 1109–1116 (2004). https://doi.org/10.1038/sj.onc.1207215

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