期刊
SCIENCE
卷 352, 期 6293, 页码 1576-1580出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aad9512
关键词
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资金
- JP Sulzberger Columbia Genome Center
- Proteomics Shared Resource
- NIH/NCI [P30 CA013696]
- National Cancer Institute [CA154293]
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000040]
- Swiss National Science Foundation [PBBSP3_146959, P300P3_151158]
- Prostate Cancer Foundation Young Investigator Award
- Swiss National Science Foundation (SNF) [PBBSP3_146959, P300P3_151158] Funding Source: Swiss National Science Foundation (SNF)
The NKX3.1 homeobox gene plays essential roles in prostate differentiation and prostate cancer. We show that loss of function of Nkx3.1 in mouse prostate results in down-regulation of genes that are essential for prostate differentiation, as well as up-regulation of genes that are not normally expressed in prostate. Conversely, gain of function of Nkx3.1 in an otherwise fully differentiated nonprostatic mouse epithelium (seminal vesicle) is sufficient for respecification to prostate in renal grafts in vivo. In human prostate cells, these activities require the interaction of NKX3.1 with the G9a histone methyltransferase via the homeodomain and are mediated by activation of target genes such as UTY (KDM6c), the male-specific paralog of UTX (KDM6a). We propose that an NKX3.1-G9a-UTY transcriptional regulatory network is essential for prostate differentiation, and we speculate that disruption of such a network predisposes to prostate cancer.
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