کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6160452 | 1249330 | 2015 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Disruption of tubular Flcn expression as a mouse model for renal tumor induction
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
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چکیده انگلیسی
The study of kidney cancer pathogenesis and its treatment has been limited by the scarcity of genetically defined animal models. The FLCN gene that codes for the protein folliculin, mutated in Birt-Hogg-Dube syndrome, presents a new target for mouse modeling of kidney cancer. Here we developed a kidney-specific knockout model by disrupting the mouse Flcn in the proximal tubules, thus avoiding homozygous embryonic lethality or neonatal mortality, and eliminating the requirement of loss of heterozygosity for tumorigenesis. This knockout develops renal cysts and early onset (6 months) of multiple histological subtypes of renal neoplasms featuring high tumor penetrance. Although the majority of the tumors were chromophobe renal cell carcinomas in affected mice under 1 year of age, papillary renal cell carcinomas predominated in the kidneys of older knockout mice. This renal neoplasia from cystic hyperplasia at 4 months to high-grade renal tumors by 16 months represented the progression of tumorigenesis. The mTOR and TGF-βsignalings were upregulated in Flcn-deficient tumors, and these two activated pathways may synergetically cause renal tumorigenesis. Treatment of knockout mice with the mTOR inhibitor rapamycin for 10 months led to the suppression oftumor growth. Thus, our model recapitulates human Birt-Hogg-Dubékidney tumorigenesis, provides a valuable tool for further study ofFlcn-deficient renal tumorigenesis, and tests new drugs/approaches to their treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 88, Issue 5, November 2015, Pages 1057-1069
Journal: Kidney International - Volume 88, Issue 5, November 2015, Pages 1057-1069
نویسندگان
Jindong Chen, Dachuan Huang, Isabelle Rubera, Kunlhlko Futami, Pengfei Wang, Peter Zlckert, Sok-Kean Khoo, Karl Dykema, Ping Zhao, David Petillo, Brian Cao, Zhongfa Zhang, Shuhui Si, Susan R. Schoen, Ximing J. Yang, Ming Zhou, Guang-Qian Xiao, Guan Wu,