title: Prostate-specific Klf6 inactivation impairs anterior prostate branching morphogenesis through increased activation of the Shh pathway.
abstract: Krüppel-like factor 6 (Klf6) belongs to a family of zinc finger transcription factors known to play a role in development and tumor suppression. Although Klf6 is highly mutated in prostate cancer, its function in prostate development is unknown. We have generated a prostate-specific Klf6-deficient mouse model and report here a novel role for Klf6 in the regulation of prostate branching morphogenesis. Importantly, our study reveals a novel relationship between Klf6 and the Shh pathway. Klf6-deficiency leads to elevated levels of hedgehog pathway components (Shh, Ptc, and Gli) and loss of their localized expression, which in turn causes impaired lateral branching.
authors.affiliation: Departments of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA.
authors.forename: Ching Ching
authors.initials: CC
authors.lastname: Leow
authors.forename: Bu-Er
authors.initials: BE
authors.lastname: Wang
authors.forename: Jed
authors.initials: J
authors.lastname: Ross
authors.forename: Sara M
authors.initials: SM
authors.lastname: Chan
authors.forename: Jiping
authors.initials: J
authors.lastname: Zha
authors.forename: Richard A D
authors.initials: RA
authors.lastname: Carano
authors.forename: Gretchen
authors.initials: G
authors.lastname: Frantz
authors.forename: Michael M
authors.initials: MM
authors.lastname: Shen
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: de Sauvage
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D053823:Hedgehog Proteins / Q000378:metabolism*; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009024:Morphogenesis; D009130:Muscle, Smooth / Q000254:growth & development; D009928:Organ Specificity; D011467:Prostate / Q000002:abnormalities / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D053823:Hedgehog Proteins; C491358:Klf6 protein, mouse; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; C465570:Shh protein, mouse; D001616:beta-Galactosidase