The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis
作者： M. Rajurkar , W. E. De Jesus-Monge , D. R. Driscoll , V. A. Appleman , H. Huang
关键词: Pancreatic cancer 、 Mediator 、 Transcription factor 、 KRAS 、 Pancreatic Intraepithelial Neoplasia 、 Cancer research 、 IKBKE 、 Endocrinology 、 Biology 、 Internal medicine 、 Carcinogenesis 、 GLI1
摘要: Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive human malignancies, is thought to be initiated by KRAS activation. Here we find that transcriptional activation mediated Gli family transcription factors, although dispensable for pancreatic development, required Kras-induced proliferation and survival in primary epithelial cells culture Kras-driven intraepithelial neoplasia PDAC formation vivo. Further, ectopic Gli1 mouse pancreas accelerates tumor formation, underscoring importance factors tumorigenesis. Interestingly, demonstrate Gli-regulated I-kappa-B kinase epsilon (IKBKE) NF-κB activity cancer show this a critical downstream mediator Gli-dependent cell transformation survival. Together, these studies requirement Kras-dependent transformation, suggest mechanism Gli-NF-κB oncogenic activation, provide genetic evidence supporting therapeutic targeting cancer.
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