Unique mutation, accelerated mTOR signaling and angiogenesis in the pulmonary cysts of Birt‐Hogg‐Dubé syndrome

摘要: Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant disorder characterized by fibrofolliculomas, renal tumors and pulmonary cysts with repeated pneumothorax. This caused mutations in the gene that encodes folliculin (FLCN). FLCN known to be involved signaling of mammalian target rapamycin (mTOR). We investigated lung a BHD patient who presented unique mutation. A 33-year-old woman visited our hospital due Histopathologic study resected demonstrated multiple epithelial cysts. An increase blood vessels was observed vicinity subpleural Genomic DNA analysis revealed heterozygous mutation at 3' end intron 5 gene. Total mRNA protein were extracted from tissue. RT-PCR sequence production exon 6-skipped mRNA. In Western blotting, band intensities phospho-mTOR, phospho-S6, phospho-Akt, hypoxia-inducible factor (HIF)-1α vascular endothelial growth (VEGF) increased compared normal lungs. strong immunostainings mTOR molecules cyst-lining cells. Collective data indicates dysregulation facilitates S6-mediated synthesis HIF-1α-mediated angiogenesis, which may contribute development this disorder.