Enhanced expression of retinoic acid receptor alpha (RARA) induces epithelial-to-mesenchymal transition and disruption of mammary acinar structures

Ayano Doi; Kosuke Ishikawa; Nao Shibata; Emi Ito; Jiro Fujimoto; Mizuki Yamamoto; Hatsuki Shiga; Hiromi Mochizuki; Yoshifumi Kawamura; Naoki Goshima; Kentaro Semba; Shinya Watanabe

doi:10.1016/j.molonc.2014.09.005

Enhanced expression of retinoic acid receptor alpha (RARA) induces epithelial-to-mesenchymal transition and disruption of mammary acinar structures

Ayano Doi, Kosuke Ishikawa, Nao Shibata, Emi Ito, Jiro Fujimoto, Mizuki Yamamoto, Hatsuki Shiga, Hiromi Mochizuki, Yoshifumi Kawamura, Naoki Goshima, Kentaro Semba^*, Shinya Watanabe

^*この研究の対応する著者

先進理工学部

研究成果: Article › 査読

22 被引用数 (Scopus)

抄録

The early steps of mammary tumorigenesis include loss of epithelial cell polarity, escape from anoikis, and acquisition of proliferative capacity. The genes responsible for these processes are predicted to be early diagnostic markers or new therapeutic targets. Here we tested 51 genes coamplified with ERBB2 in the 17q12-21 amplicon for these tumorigenic activities using an MCF10A 3D culture-based screening system. We found that overexpression of retinoic acid receptor α (RARA) disrupted normal acinar structure and induced epithelial-to-mesenchymal transition (EMT). The mRNA levels of known EMT-inducing factors, including SLUG, FOXC2, ZEB1, and ZEB2, were significantly increased upon RARA overexpression. Knockdown of ZEB1 suppressed the RARA-mediated EMT phenotype. These results suggest that overexpression of RARA enhances malignant transformation during mammary tumorigenesis.

本文言語	English
ページ（範囲）	355-364
ページ数	10
ジャーナル	Molecular Oncology
巻	9
号	2
DOI	https://doi.org/10.1016/j.molonc.2014.09.005
出版ステータス	Published - 2015 2月 1

ASJC Scopus subject areas

分子医療
遺伝学
腫瘍学
癌研究

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10.1016/j.molonc.2014.09.005

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引用スタイル

Doi, A., Ishikawa, K., Shibata, N., Ito, E., Fujimoto, J., Yamamoto, M., Shiga, H., Mochizuki, H., Kawamura, Y., Goshima, N., Semba, K., & Watanabe, S. (2015). Enhanced expression of retinoic acid receptor alpha (RARA) induces epithelial-to-mesenchymal transition and disruption of mammary acinar structures. Molecular Oncology, 9(2), 355-364. https://doi.org/10.1016/j.molonc.2014.09.005

Doi, A, Ishikawa, K, Shibata, N, Ito, E, Fujimoto, J, Yamamoto, M, Shiga, H, Mochizuki, H, Kawamura, Y, Goshima, N, Semba, K & Watanabe, S 2015, 'Enhanced expression of retinoic acid receptor alpha (RARA) induces epithelial-to-mesenchymal transition and disruption of mammary acinar structures', Molecular Oncology, vol. 9, no. 2, pp. 355-364. https://doi.org/10.1016/j.molonc.2014.09.005

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abstract = "The early steps of mammary tumorigenesis include loss of epithelial cell polarity, escape from anoikis, and acquisition of proliferative capacity. The genes responsible for these processes are predicted to be early diagnostic markers or new therapeutic targets. Here we tested 51 genes coamplified with ERBB2 in the 17q12-21 amplicon for these tumorigenic activities using an MCF10A 3D culture-based screening system. We found that overexpression of retinoic acid receptor α (RARA) disrupted normal acinar structure and induced epithelial-to-mesenchymal transition (EMT). The mRNA levels of known EMT-inducing factors, including SLUG, FOXC2, ZEB1, and ZEB2, were significantly increased upon RARA overexpression. Knockdown of ZEB1 suppressed the RARA-mediated EMT phenotype. These results suggest that overexpression of RARA enhances malignant transformation during mammary tumorigenesis.",

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note = "Funding Information: We would like to acknowledge the secretarial assistance of Kumiko Semba. This research was partially supported by Japan Society for the Promotion of Science KAKENHI 23241064 and a grant for Translational Research Program: Achievement of personalized medicine and acceleration of anti-cancer drug development by using gene expression analysis technology from the New Energy and Industrial Technology Development Organization (NEDO). Publisher Copyright: {\textcopyright} 2014 Federation of European Biochemical Societies.",

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