Prostate-specific Klf6 inactivation impairs anterior prostate branching morphogenesis through increased activation of the Shh pathway.
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.
Leow
Ching Ching
CC
Departments of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA.
Wang
Bu-Er
BE
Ross
Jed
J
Chan
Sara M
SM
Zha
Jiping
J
Carano
Richard A D
RA
Frantz
Gretchen
G
Shen
Michael M
MM
de Sauvage
Frederic J
FJ
Gao
Wei-Qiang
WQ
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
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