alexa Molecular Profiling Journals|OMICS International|Journal Of Molecular Biomarkers And Diagnosis

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Molecular Profiling Journals

Molecular profiling refers to the study of specific patterns, or signature, of proteins, mRNA, DNA. Molecular profiling of PTC offers a valuable tool for identifying genes that can be used as diagnostic and prognostic markers. Molecular profiling of papillary thyroid carcinomas samples and paired controls identified 177 differentially expressed genes (98 upregulated and 79 downregulated). The upregulation of potential biomarkers was verified in expanded sample sets by qRT-PCR and immunohistochemisty, and included arachidonic acid 5-lipoxygenase (ALOX5), urokinase plasminogen activator and its receptor (uPA/uPAR) and kallikreins 7 and 10 (KLK7/KLK10). ALOX5 expression was elevated in PTC (22.57 fold) and demonstrated a direct correlation with tumor invasiveness. Transfection of ALOX5 into the PTC cell line, BCPAP, resulted in increased collagenase activity, MMP-9 secretion and invasiveness.Transfection of ALOX5 into the PTC cell line, BCPAP, resulted in increased collagenase activity, MMP-9 secretion and invasiveness. Inhibitors of MMP-9 and ALOX5 reversed the ALOX5-enhanced invasion. uPA and uPAR transcription was increased in PTC (2.4 and 10.1 fold, respectively) and in BCPAP, relative to a normal thyroid cell line. siRNA-mediateddownregulation of uPAR in BCPAP cells resulted in decreased activity in the FAK/PI3K/Aktsignaling pathway, proliferation, clonigenicity and migration/invasion. KLK7 and KLK10 RNA expression in PTC was upregulated (21.0 and 22.0 fold) and immunohistochemical analysis on patient samples revealed increased and coordinated expression. These data provide new evidence of ALOX5 and uPA/uPAR system’s functional roles in PTC invasion/metastasis, and demonstrate their attractiveness as molecular biomarkers and therapeutic targets. The role of KLKs in PTC pathogenesis is currently under investigation. (Jan Geliebter, Molecular profiling of papillary thyroid cancer identifies functional biomarkers)
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Last date updated on July, 2014

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