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Hoxb13 regulatory elements mediate transgene expression during prostate organogenesis and carcinogenesis
Author(s) -
McMullin Ryan P.,
Mutton Laura N.,
Bieberich Charles J.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21870
Subject(s) - biology , prostate cancer , carcinogenesis , regulation of gene expression , prostate , androgen , cancer research , androgen receptor , transgene , reporter gene , gene expression , gene , genetics , endocrinology , cancer , hormone
The prostate requires androgens for development and homeostasis. Prostate cancer shares this dependence, however progression to androgen‐independence is common after androgen deprivation. There is considerable interest in achieving therapeutic gene expression after androgen ablation using prostate‐specific promoters. Paradoxically, known prostate‐restricted cis ‐regulatory elements are androgen dependent. Hoxb13 expression is restricted in adults to the prostate and colon, and robust Hoxb13 expression persists after castration. To locate regulatory elements conferring this expression pattern, a lacZ reporter was inserted into the Hoxb13 locus on a mouse genomic bacterial artificial chromosome. In transgenic mice, this construct recapitulated the Hoxb13 expression pattern, including expression after castration. Reporter gene activity was maintained during carcinogenesis in a prostate cancer model. Hoxb13 cis ‐regulatory elements provide a powerful tool to achieve androgen‐independent transgene expression in the prostate and distal colon‐specific expression in the gastrointestinal tract. These data establish a framework for high‐resolution analyses of factors regulating Hoxb13 . Developmental Dynamics 238:664–672, 2009. © 2009 Wiley‐Liss, Inc.