Premium
PLZF regulates Pbx1 transcription and Pbx1–HoxC8 complex leads to androgen‐independent prostate cancer proliferation
Author(s) -
Kikugawa Tadahiko,
Kinugasa Yumi,
Shiraishi Ken,
Nanba Daisuke,
Nakashiro Kohichi,
Tanji Nozomu,
Yokoyama Masayoshi,
Higashiyama Shigeki
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20443
Subject(s) - du145 , biology , gene knockdown , prostate cancer , cancer research , microarray analysis techniques , gene expression , endocrinology , microbiology and biotechnology , medicine , cell culture , lncap , gene , cancer , genetics
Abstract BACKGROUND Promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor and negative regulator of the cell cycle, has been characterized as a prostatic androgen‐responsive gene. DU145 cells show androgen‐independent growth and lack PLZF gene expression. METHODS We analyzed PLZF‐regulating genes by DNA microarray using DU145 cells infected with LacZ‐ or PLZF‐carrying adenoviruses. RESULTS DNA microarray revealed that Pbx1 is a prominent suppressed gene in PLZF‐overexpressing DU145 cells. Androgen receptor (AR)‐expressing DU145 cells recovered androgen‐dependent PLZF expression and subsequent repression of Pbx1 expression. Immunoprecipitation of Pbx1 in DU145 cells revealed a Pbx1‐HoxC8 heterocomplex. siRNAs for Pbx1 and HoxC8 knocked downexpression of each, and this suppressed androgen‐independent cell growth. Double knockdown of both Pbx1 and HoxC8 suppressed cell growth much more significantly. CONCLUSIONS Androgen‐independent cell line DU145 cells lack PLZF gene expression, resulting in the upregulation of Pbx1 and HoxC8 expression. The Pbx1–HoxC8 heterocomplex may lead to androgen‐independent growth in prostate cancer. Prostate 66: 1092‐1099, 2006. © 2006 Wiley‐Liss, Inc.