ABSTRACT
Stimulation of BxPC-3, Panc-1, and MIA PaCA-2 pancreatic cancer cells with EGF, HGF, FGF-1, FGF-2, FGF-7, and FGF-10 growth factors caused changes in the expression of master genes regulating pancreatic development (SOX9, HNF3b, GATA-4, GATA-6, and HES1). This, in turn, caused changes in the expression profile of important transcription factors, embryonic development regulators. It was also found that the master genes belonging to the same family may cause opposite effects (suppression or enhancement of expression of a particular transcriptional regulator) in the same cell line.
Subject(s)
Gene Expression Regulation, Neoplastic/drug effects , Intercellular Signaling Peptides and Proteins/pharmacology , Pancreatic Neoplasms/pathology , Biomarkers, Tumor/genetics , Carcinogenesis/drug effects , Carcinogenesis/genetics , Cell Line, Tumor , Humans , Pancreatic Neoplasms/geneticsABSTRACT
Fibroblast growth factors (FGF) - growth factors that regulate many important biological processes, including proliferation and differentiation of embryonic cells during organogenesis. In this review, we will summarize current information about the involvement of FGFs in the pancreas organogenesis. Pancreas organogenesis is a complex process, which involves constant signaling from mesenchymal tissue. This orchestrates the activation of various regulator genes at specific stages, determining the specification of progenitor cells. Alterations in FGF/FGFR signaling pathway during this process lead to incorrect activation of the master genes, which leads to different pathologies during pancreas development. Understanding the full picture about role of FGF factors in pancreas development will make it possible to more accurately understand their role in other pathologies of this organ, including carcinogenesis.
Subject(s)
Enteroendocrine Cells/metabolism , Fibroblast Growth Factors/genetics , Gene Expression Regulation, Developmental , Organogenesis/genetics , Pancreas/metabolism , Receptor, Fibroblast Growth Factor, Type 1/genetics , Animals , Cell Differentiation , Cell Lineage/genetics , Enteroendocrine Cells/cytology , Fibroblast Growth Factors/classification , Fibroblast Growth Factors/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Pancreas/cytology , Pancreas/growth & development , Receptor, Fibroblast Growth Factor, Type 1/metabolism , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Signal Transduction , Trans-Activators/genetics , Trans-Activators/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Fibroblast growth factors belong to a family of growth factors that are involved in various processes in organism and have a wide range of biological functions. Specifically for pancreas, FGFs are important during both organogenesis and carcinogenesis. One of the main characteristic of pancreatic cancer, is it close interaction between cancer and stromal cells via different factors, including FGF. Pathological changes in FGF/FGFR signaling pathway is a complex process. The remodeling effects and stimulation of tumor growth are mostly depend not only on types of receptors, but also from their isoforms. FGF/FGFR signaling pathway is a perspective specific marker for cancer progression, and a potential drug target, which can be used for treatment of pancreatic cancer.
Subject(s)
Fibroblast Growth Factors/metabolism , Neoplasm Proteins/metabolism , Pancreatic Neoplasms/metabolism , Receptors, Fibroblast Growth Factor/metabolism , Animals , Humans , Pancreatic Neoplasms/therapyABSTRACT
Health service today is on the verge of broad changes. The intensive practical application of the achievements of genomics, proteomics, metabolomics and bioinformatics has significantly deepened and continues to deepen our view of the pathological processes taking place at a level of biostructures. In the nearest future this progress will give medical practitioners the opportunity to focus on a subclinical stage of the disease, i.e. on the earliest stages of the pathological process. This will require the prediction of disease development risks, subclinical diagnostics with the precise staging of the pathological process, and, finally, the application as early as possible of targeted pharmacotherapeutic methods in order to prevent the manifestation of the disease or its progression into more severe stages. All these principles create the framework of a fundamentally new "3P" strategy in medicine: predictive, preventive and personalized medicine.
Subject(s)
Molecular Diagnostic Techniques/trends , Precision Medicine , Preventive Medicine/methods , Computational Biology , Genomics , Humans , Mutation , Preventive Medicine/trends , ProteomicsABSTRACT
Proteomics is a science which studies proteins of the body, interactions of proteins and their biological functions. Today, it is an essential partner in establishing preclinical diagnosis protocols. In conjunction with other sciences such as genomics and bioinformatics it will be possible to diagnose diseases on the earliest stages before its clinical onset or to gain the dynamics of pathological processes in the body and response to drug therapy. This article discusses general aspects of proteomics as well as special ones on the basis of models of cardiac diseases and cancer.
