PHD3 regulates differentiation, tumour growth and angiogenesis in pancreatic cancer
In: British journal of cancer, Jg. 103 (2010), Heft 10, S. 1571-1579
Online
academicJournal
- print, 3/4 p
Zugriff:
PURPOSE: Tumour hypoxia activates hypoxia-inducible factor-1 (HIF-1) and indluences angiogenesis, cell survival and invasion. Prolyl hydroxylase-3 (PHD3) regulates degradation of HIF-1α. The effects of PHD3 in tumour growth are largely unknown. EXPERIMENTAL DESIGN: PHD3 expression was analysed in human pancreatic cancer tissues and cancer cell lines by real-time quantitative PCR and immunohistochemistry. PHD3 overexpression was established by stable transfection and downregulation by short interfering RNA technology. VEGF was quantified by enzyme-linked immunosorbent assay. Matrigel invasion assays were performed to examine tumour cell invasion. Apoptosis was measured by annexin-V staining and caspase-3 assays. The effect of PHD3 on tumour growth in vivo was evaluated in an established orthotopic murine model. RESULTS: PHD3 was upregulated in well-differentiated human tumours and cell lines, and regulated hypoxic VEGF secretion. PHD3 overexpression mediated tumour cell growth and invasion by induction of apoptosis in a nerve growth factor-dependent manner by the activation of caspase-3 and phosphorylation of focal adhesion kinase HIF-1 independently. In vivo, PHD3 inhibited tumour growth by abrogation of tumour angiogenesis. CONCLUSION: Our results indicate essential functions of PHD3 in tumour growth, apoptosis and angiogenesis and through HIF-1-dependent and HIF-1-independent pathways.
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PHD3 regulates differentiation, tumour growth and angiogenesis in pancreatic cancer
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Autor/in / Beteiligte Person: | SU, Y ; LOOS, M ; GIESE, N ; HINES, O. J ; DIEBOLD, I ; GÖRLACH, A ; METZEN, E ; PASTOREKOVA, S ; FRIESS, H ; BÜCHLER, P |
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Zeitschrift: | British journal of cancer, Jg. 103 (2010), Heft 10, S. 1571-1579 |
Veröffentlichung: | Basingstoke: Nature Publishing Group, 2010 |
Medientyp: | academicJournal |
Umfang: | print, 3/4 p |
ISSN: | 0007-0920 (print) |
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