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    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; INVASION ; CELL ; Germany ; human ; IN-VIVO ; GENE-EXPRESSION ; transcription ; TISSUE ; RELEASE ; COMPLEX ; COMPLEXES ; TRANSCRIPTION FACTOR ; TISSUES ; tumour ; DOWN-REGULATION ; treatment ; cytokines ; TRANSCRIPTION FACTORS ; LESIONS ; immunohistochemistry ; VECTOR ; PCR ; SIGNALING PATHWAY ; CANCER-CELLS ; EXTRACELLULAR-MATRIX ; MAMMALIAN-CELLS ; adenocarcinoma ; GROWTH-FACTOR-BETA ; OVEREXPRESSION ; real-time PCR ; pancreatic cancer ; microenvironment ; CYTOKINE ; MATRIX ; ONCOLOGY ; PANCREATIC-CANCER ; DUCTAL ADENOCARCINOMA ; INCREASE ; extracellular matrix ; regulation ; ENHANCED EXPRESSION ; REAL-TIME ; TGF-BETA ; TGF-beta 1 ; LEVEL ; analysis ; pancreatic ; pancreatic adenocarcinoma ; coculture ; quantitative ; FULL-LENGTH ; transforming growth factor ; pancreatic ductal adenocarcinoma ; beta-tumour microenvironment ; CHEMICAL-MODIFICATIONS ; INDIAN-HEDGEHOG ; matrix metalloprotease ; osteonectin ; stellate cells ; STELLATE-CELLS
    Abstract: Recent evidence suggests that Runt-related transcription factors play a role in different human tumours. In the present study, the localisation of the Runt-related transcription factor-2 (Runx2), its transcriptional activity, as well as its regulation of expression was analysed in human pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time PCR and immunohistochemistry were used for Runx2 expression and localisation analysis. Runt-related transcription factor-2 expression was silenced using specific siRNA oligonucleotides in pancreatic cancer cells (Panc-1) and immortalised pancreatic stellate cells (IPSCs). Overexpression of Runx2 was achieved using a full-length expression vector. TGF-beta 1, BMP2, and other cytokines were assessed for their potential to regulate Runx2 expression. There was a 6.1-fold increase in median Runx2 mRNA levels in PDAC tissues compared to normal pancreatic tissues (P〈0.0001). Runt-related transcription factor-2 was localised in pancreatic cancer cells, tubular complexes, and PanIN lesions of PDAC tissues as well as in tumour-associated fibroblasts/stellate cells. Coculture of IPSCs and Panc-1 cells, as well as treatment with TGF-beta 1 and BMP2, led to increased Runx2 expression in Panc-1 cells. Runt-related transcription factor-2 overexpression was associated with decreased MMPI release as well as decreased growth and invasion of Panc-1 cells. These effects were reversed by Runx2 silencing. In conclusion, Runx2 is overexpressed in PDAC, where it is regulated by certain cytokines such as TGF-beta 1 and BMP2 in an auto- and paracrine manner. In addition, Runx2 has the potential to regulate the transcription of extracellular matrix modulators such as SPARC and MMPI, thereby influencing the tumour microenvironment
    Type of Publication: Journal article published
    PubMed ID: 17876328
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