title: GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor.
abstract: Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from anandrogen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Guangchun
authors.initials: G
authors.lastname: Chen
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Goto
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sakamoto
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Tanaka
authors.forename: Eri
authors.initials: E
authors.lastname: Matsubara
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: C410798:AR protein, human; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D011944:Receptors, Androgen; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1