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      Investigating the role of transcription factors of pancreas development in pancreatic cancer.

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          Abstract

          Pancreatic cancer (PC) is the seventh most common cause of cancer-related deaths worldwide that kills more than 300,000 people every year. Prognosis of PC is very poor with a five-year survival rate about 5%. The most common and highly observed type of PC is pancreatic ductal adenocarcinoma (PDAC). It is preceded by the progression of precursor lesions such as Pancreatic Intraepithelial Neoplasia (PanIN), Intraductal Papillary Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN). PanIN is the most common among these premalignant lesions. Genes orchestrating the origin and differentiation of cells during organogenesis have the tendency to produce tumor cells in response to activating or inactivating mutations. Based on the following premise, we discuss the role of transcription factors (TFs) of pancreas development and cell fate differentiation in PC. Pancreas/duodenum homeobox protein 1 (PDX1), Pancreas transcription factor 1 subunit alpha (PTF1A), Nuclear receptor subfamily 5 group A member 2 (NR5A2), Hepatocyte nuclear factor 1-alpha (HNF1A) and Hepatocyte nuclear factor 1-beta (HNF1B) play vital role in the development and differentiation of pancreatic precursor cells. Mutated KRAS induces abnormalities in the regular function of these TFs which in turn cause abnormal cell growth and proliferation that leads to cancer. Thus, these TFs are highly susceptible for the origin of PC. Therefore, we propose that these TFs can be treated as therapeutic targets for the development of anticancer drugs.

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          Author and article information

          Journal
          Pancreatology
          Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
          Elsevier BV
          1424-3911
          1424-3903
          Mar 2018
          : 18
          : 2
          Affiliations
          [1 ] Center for Interdisciplinary Research in Basic Science, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
          [2 ] Department of Biochemistry, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
          [3 ] Center for Interdisciplinary Research in Basic Science, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India. Electronic address: mihassan@jmi.ac.in.
          Article
          S1424-3903(17)30912-2
          10.1016/j.pan.2017.12.013
          29289465
          2a36a91c-e669-432c-b02a-40f642f4b789
          History

          Protein-protein interaction,Therapeutic targets,Transcription factors,Developmental pathways,Pancreatic cancer

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