FOR 527:  Susceptibility Factors of Tumorigenesis

• Subject Area: Medicine
• Term: from 2004 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5470647

The Research Unit focuses on the investigation of the molecular factors responsible for tumor initiation and progression. In general, the term "susceptibility" describes the vulnerability of individuals and biological systems to the process of tumorigenesis. Individual susceptibility factors determine the extent of this vulnerability. Known susceptibility factors are:
-- The activities of toxicating and detoxifying enzymes of xenobiotic metabolism (they affect the cellular concentration of genotoxic substances).
-- DNA repair mechanisms (they determine the cellular susceptibility for the accumulation of mutations and damage-induced cytotoxicity).
-- The activity of oncogenes and tumor suppressor genes (enabling a coordinated process of proliferation and apoptosis, as well as controlling genomic integrity).
Unravelling the molecular mechanisms that determine susceptibility is the common goal of all projects involved. In this approach, the Research Unit combines toxicological and molecular aspects of tumour biology. Of special interest are the key factors VHL, PTEN, HER-2, AML-ETO, and small GTPases. Another focal point is the investigation of repair mechanisms for DNA damaged by oxidative stress and alkylating agents. Furthermore, detoxification of chemically reactive substances (especially epoxides) are key mechanisms that protect against cancer. To understand cellular susceptibility, their characterisation on the molecular level is of specific importance.

• DFG Programme: Research Units

Projects

• Alternative Tumorsuppressionsmechanismen bei Bronchialkarzinomen - Molekulare Charakterisierung und Möglichkeiten der therapeutischen Modulation (Applicant Schuler, Martin )
• Bedeutung der oxidativen DNA-Schädigung für die Tumorentstehung (Applicant Epe, Bernd )
• Cisplatin-induzierte DNA-Läsionen und deren Bedeutung für die chemo-therapeutische Behandlung (Applicant Köberle, Beate )
• Die Bedeutung von Epoxidhydrolasen für die Suszeptibilität gegenüber chemischen Kanzerogenen (Applicant Oesch, Franz )
• Einfluss von DNA-Reparatur auf Genotoxin-Resistenz und Apoptose induziert durch alkylierende Agenzien (Applicant Kaina, Bernd )
• In vivo Charakterisierung von sensibilisierenden und protektiven Suszeptibilitätsfaktoren der Tumorgenese (Applicant Bockamp, Ernesto )
• Kooperative Schritte in der VHL-abhängigen Tumorentstehung (Applicant Lausch, Ekkehart Ullrich )
• TH2 Zytokine in der Pathogenese des Colitis-assoziierten Colonkarzinoms: Molekulare und immuntoxikologische Untersuchungen (Applicant Wirtz, Stefan )
• Zelluläre Antworten auf gentoxische Expositionen: DNA-schadensabhängige und DNA-schadensunabhängige Mechanismen (Applicant Fritz, Gerhard )
• Zentrale Verwaltung (Applicant Kaina, Bernd )
• Zentralprojekt - Ergänzungsprojekt zur Versuchstierhaltung und Generierung von transgenen und knockdown Mausmodellen (Applicant Bockamp, Ernesto )

• Spokesperson: Professor Dr. Bernd Kaina