کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2176192 | 1093866 | 2006 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation
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کلمات کلیدی
CREDAPICre-recombinase4,6-diamidino-2-phenylindole - 4،6-دیامیدین-2-فنیلینولCell differentiation - تمایز سلولیCell proliferation - تکثیر سلولیProstate cancer - سرطان پروستاتcytokeratin - سیتوکراتینMouse models - مدل موشNotch - نچBenign prostatic hyperplasia - هیپرپلازی خوش خیم پروستاتBPH - هیپرپلازی خوش خیم پروستات یا BPHProstate development - پیشرفت پروستات
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. Using a transgenic cell ablation approach, we found in our previous study that cells expressing Notch1 are crucial for prostate early development and re-growth. Here, we further define the role of Notch signaling in regulating prostatic epithelial cell growth and differentiation using biochemical and genetic approaches in ex vivo or in vivo systems. Treatment of developing prostate grown in culture with inhibitors of gamma-secretase/presenilin, which is required for Notch cleavage and activation, caused a robust increase in proliferation of epithelial cells co-expressing cytokeratin 8 and 14, lack of luminal/basal layer segregation and dramatically reduced branching morphogenesis. Using conditional Notch1 gene deletion mouse models, we found that inactivation of Notch1 signaling resulted in profound prostatic alterations, including increased tufting, bridging and enhanced epithelial proliferation. Cells within these lesions co-expressed both luminal and basal cell markers, a feature of prostatic epithelial cells in predifferentiation developmental stages. Microarray analysis revealed that the gene expression in a number of genetic networks was altered following Notch1 gene deletion in prostate. Furthermore, expression of Notch1 and its effector Hey-1 gene in human prostate adenocarcinomas were found significantly down-regulated compared to normal control tissues. Taken together, these data suggest that Notch signaling is critical for normal cell proliferation and differentiation in the prostate, and deregulation of this pathway may facilitate prostatic tumorigenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 290, Issue 1, 1 February 2006, Pages 66-80
Journal: Developmental Biology - Volume 290, Issue 1, 1 February 2006, Pages 66-80
نویسندگان
Xi-De Wang, Ching Ching Leow, Jiping Zha, Zhijun Tang, Zora Modrusan, Freddy Radtke, Michel Aguet, Frederic J. de Sauvage, Wei-Qiang Gao,