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

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
9
2
DOI
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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