Estrogen Regulates Tumor Growth Through a Nonclassical Pathway that Includes the Transcription Factors ERβ and KLF5

• DOI: 10.1126/scisignal.2001551
• Publication Date: 2011-04-12T21:42:04Z
• Authors: Yuka Nakajima; Kensuke Akaogi; Takashi Suzuki; Asami Osakabe; Chie Yamaguchi; Nanae Sunahara; Junji Ishida; Koichiro Kako; Sonoko Ogawa; Tetsuya Fujimura; Yukio Homma; Akiyoshi Fukamizu; Akiko Murayama; Keiji Kimura; Satoshi Inoue; Junn Yanagisawa
• Keywords: Transcription

Clinical evidence suggests that antiestrogens inhibit the development of androgen-insensitive prostate cancer. Here, we show estrogen receptor β (ERβ) mediates inhibition by antiestrogen ICI 182,780 (ICI) and its enhancement estrogen. ERβ associated with gene promoters through tumor-suppressing transcription factor KLF5 (Krüppel-like zinc finger 5). treatment increased recruitment coactivator CBP [CREB (adenosine 3',5'-monophosphate response element-binding protein)-binding protein] to promoter FOXO1 KLF5, which enhanced FOXO1. The increase in abundance led anoikis cancer cells, thereby suppressing tumor growth. In contrast, induced formation complexes containing ERβ, ubiquitin ligase WWP1 (WW domain E3 protein 1), resulting ubiquitination degradation KLF5. combined presence positively correlated longer cancer-specific survival patients. Our results demonstrate estrogens affect growth ERβ-mediated regulation