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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Bone Morphogenetic Protein 4 / metabolism
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Gene Deletion
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Gene Expression Regulation, Developmental
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Gene Silencing*
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Hedgehog Proteins / metabolism*
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Kruppel-Like Factor 6
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Kruppel-Like Transcription Factors / deficiency
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Kruppel-Like Transcription Factors / genetics*
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Kruppel-Like Transcription Factors / metabolism
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Male
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Mice
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Morphogenesis*
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Muscle, Smooth / growth & development
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Organ Specificity
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Prostate / abnormalities
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Prostate / growth & development*
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Prostate / metabolism*
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Prostate / pathology
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Signal Transduction*
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Up-Regulation / genetics
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beta-Galactosidase / metabolism
Substances
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Bmp4 protein, mouse
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Bone Morphogenetic Protein 4
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Hedgehog Proteins
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Klf6 protein, mouse
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Kruppel-Like Factor 6
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Kruppel-Like Transcription Factors
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Proto-Oncogene Proteins
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Shh protein, mouse
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beta-Galactosidase