Neue Studie zur Behandlung von Bauchspeicheldrüsenkrebs
03.05.2012 um 14:30In groben Zügen.
Wissenschaftler haben ein Gen entdeckt, das vielleicht neue Behandlungsmethoden beim Kampf gegen das duktale Adenokarzinom der Bauchspeicheldrüse ermöglichen könnte.
Dieser Krebs wird meist erst spät entdeckt und hat eine schlechte Prognose.
USP9X kann der Studie zufolge die Entwicklung des Krebses unterdrücken.
Genaueres für die, die es interessiert:
Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations1, 2, 3, 4 in addition to numerous lower frequency genetic events of uncertain significance5. Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis6, 7 in a mouse model of pancreatic ductal preneoplasia8 to identify genes that cooperate with oncogenic KrasG12D to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia9, we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2′-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with KrasG12D to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA.
Den ganzen Artikel gibts bei "Nature", ist allerdings kostenpflichtig.
Ich schau aber nachher noch mal in der Pubmed.
Quelle: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11114.html
Wissenschaftler haben ein Gen entdeckt, das vielleicht neue Behandlungsmethoden beim Kampf gegen das duktale Adenokarzinom der Bauchspeicheldrüse ermöglichen könnte.
Dieser Krebs wird meist erst spät entdeckt und hat eine schlechte Prognose.
USP9X kann der Studie zufolge die Entwicklung des Krebses unterdrücken.
Genaueres für die, die es interessiert:
Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations1, 2, 3, 4 in addition to numerous lower frequency genetic events of uncertain significance5. Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis6, 7 in a mouse model of pancreatic ductal preneoplasia8 to identify genes that cooperate with oncogenic KrasG12D to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia9, we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2′-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with KrasG12D to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA.
Den ganzen Artikel gibts bei "Nature", ist allerdings kostenpflichtig.
Ich schau aber nachher noch mal in der Pubmed.
Quelle: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11114.html