دورية أكاديمية
أعرض في EDS

NF-kappaB functions as a tumour promoter in inflammation-associated cancer.

التفاصيل البيبلوغرافية
العنوان: NF-kappaB functions as a tumour promoter in inflammation-associated cancer.
المؤلفون: Pikarsky E; Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. peli@hadassah.org.il, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y
المصدر: Nature [Nature] 2004 Sep 23; Vol. 431 (7007), pp. 461-6. Date of Electronic Publication: 2004 Aug 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Carcinoma, Hepatocellular/*complications , Carcinoma, Hepatocellular/*metabolism , Inflammation/*complications , Inflammation/*metabolism , NF-kappa B/*metabolism, ATP Binding Cassette Transporter, Subfamily B/deficiency ; ATP Binding Cassette Transporter, Subfamily B/genetics ; ATP-Binding Cassette Transporters/genetics ; Animals ; Carcinoma, Hepatocellular/etiology ; Carcinoma, Hepatocellular/pathology ; Chronic Disease ; Disease Progression ; Hepatitis/complications ; Hepatitis/etiology ; Hepatitis/metabolism ; Hepatitis/pathology ; Hepatocytes/metabolism ; Hepatocytes/pathology ; I-kappa B Proteins/metabolism ; Inflammation/pathology ; Liver/metabolism ; Liver/pathology ; Mice ; Mice, Knockout ; Paracrine Communication ; Tumor Necrosis Factor-alpha/metabolism
مستخلص: The causes of sporadic human cancer are seldom recognized, but it is estimated that carcinogen exposure and chronic inflammation are two important underlying conditions for tumour development, the latter accounting for approximately 20% of human cancer. Whereas the causal relationship between carcinogen exposure and cancer has been intensely investigated, the molecular and cellular mechanisms linking chronic inflammation to tumorigenesis remain largely unresolved. We proposed that activation of the nuclear factor kappaB (NF-kappaB), a hallmark of inflammatory responses that is frequently detected in tumours, may constitute a missing link between inflammation and cancer. To test this hypothesis, we studied the Mdr2-knockout mouse strain, which spontaneously develops cholestatic hepatitis followed by hepatocellular carcinoma, a prototype of inflammation-associated cancer. We monitored hepatitis and cancer progression in Mdr2-knockout mice, and here we show that the inflammatory process triggers hepatocyte NF-kappaB through upregulation of tumour-necrosis factor-alpha (TNFalpha) in adjacent endothelial and inflammatory cells. Switching off NF-kappaB in mice from birth to seven months of age, using a hepatocyte-specific inducible IkappaB-super-repressor transgene, had no effect on the course of hepatitis, nor did it affect early phases of hepatocyte transformation. By contrast, suppressing NF-kappaB inhibition through anti-TNFalpha treatment or induction of IkappaB-super-repressor in later stages of tumour development resulted in apoptosis of transformed hepatocytes and failure to progress to hepatocellular carcinoma. Our studies thus indicate that NF-kappaB is essential for promoting inflammation-associated cancer, and is therefore a potential target for cancer prevention in chronic inflammatory diseases.
التعليقات: Comment in: Nature. 2004 Sep 23;431(7007):405-6. (PMID: 15385993)
Comment in: J Hepatol. 2005 Apr;42(4):610-1. (PMID: 16715553)
المشرفين على المادة: 0 (ATP Binding Cassette Transporter, Subfamily B)
0 (ATP-Binding Cassette Transporters)
0 (I-kappa B Proteins)
0 (NF-kappa B)
0 (Tumor Necrosis Factor-alpha)
9EI49ZU76O (multidrug resistance protein 3)
تواريخ الأحداث: Date Created: 20040827 Date Completed: 20041005 Latest Revision: 20220316
رمز التحديث: 20231215
DOI: 10.1038/nature02924
PMID: 15329734
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/nature02924