Singh S R, Zhen W, Zheng Z, Wang H, Oh S-W, Liu W, Zbar B, Schmidt L S, Hou S X
Mouse Cancer Genetics Program, National Institutes of Health, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Oncogene. 2006 Sep 28;25(44):5933-41. doi: 10.1038/sj.onc.1209593. Epub 2006 Apr 24.
Birt-Hogg-Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The BHD locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (BHD) were identified in a panel of BHD families. Using RNA interference to decrease expression of the Drosophila BHD homolog (DBHD), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of DBHD gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either unpaired (upd) or decapentaplegic (dpp). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human.
Birt-Hogg-Dubé综合征（BHD）是一种罕见的遗传性基因皮肤病，其特征为毛囊错构瘤、肾肿瘤和自发性气胸。通过连锁分析将BHD基因座定位于17号染色体短臂11.2区，并在一组BHD家族中鉴定出一个新基因（BHD）的种系突变。利用RNA干扰降低果蝇BHD同源基因（DBHD）的表达，我们已经证明DBHD是果蝇睾丸中雄性生殖系干细胞（GSC）维持所必需的。DBHD基因活性的降低抑制了与未配对（upd）或骨形态发生蛋白（dpp）过表达相关的GSC过度增殖表型。进一步的遗传相互作用实验表明，DBHD在JAK/STAT和Dpp信号转导途径的下游或与之平行调节GSC的维持。这些发现表明，BHD蛋白可能通过调节人类干细胞来调控肿瘤发生。
