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Aryl hydrocarbon nuclear translocator (hypoxia inducible factor 1β) activity is required more during early than late tumor growth
Molecular carcinogenesis, 2010-02, Vol.49 (2), p.157-165
Shi, S.
Yoon, D.Y.
Hodge-Bell, K.
Huerta-Yepez, S.
Hankinson, O.
2010
Details
Autor(en) / Beteiligte
Shi, S.
Yoon, D.Y.
Hodge-Bell, K.
Huerta-Yepez, S.
Hankinson, O.
Titel
Aryl hydrocarbon nuclear translocator (hypoxia inducible factor 1β) activity is required more during early than late tumor growth
Ist Teil von
Molecular carcinogenesis, 2010-02, Vol.49 (2), p.157-165
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2010
Link zum Volltext
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
c4 is a derivative of the mouse hepatoma cell line, Hepa‐1, that harbors a mutation in the aryl hydrocarbon receptor nuclear translocator gene (Arnt, or hypoxia inducible factor 1β [HIF‐1β]) leading to loss of activity. Clone 3 cells were generated by introducing a doxycycline‐repressible Arnt expression vector into c4 cells. Clone 3 cells were injected subcutaneously into immunosuppressed mice, which were treated with doxycyline (a) throughout the growth of the subsequent tumor xenografts, or (b) from day 7 through to the end of the experiment (day 30), or not treated (c). Tumors in all groups grew exponentially between days 14 and 30, and at rates that were indistinguishable from each other. However, tumors in group a were smaller than those of the other two groups throughout the measurable growth period, while tumor volumes in groups b and c were not significantly different from each other. The degrees of vascularity and apoptosis did not correlate with the differences in degrees of growth between the different groups. Thus, Arnt is required during the early stages of growth of the tumors but less in later stages. Since Arnt does not detectably effect the growth kinetics of Hepa‐1 cells either during hypoxia or normoxia, this requirement is unlikely to reflect a direct effect of Arnt on cell proliferation, and is therefore probably a consequence of altered interaction(s) between the tumor cells and the host. These studies suggest that Arnt (and HIF‐1α/HIF‐2α) inhibitors will be particularly effective against smaller tumors, including micrometastases. © 2009 Wiley‐Liss, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0899-1987
eISSN: 1098-2744
DOI: 10.1002/mc.20585
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2938742
Format
–
Schlagworte
Animals
,
aryl hydrocarbon receptor nuclear translocator (ARNT)
,
Aryl Hydrocarbon Receptor Nuclear Translocator - physiology
,
Base Sequence
,
Blotting, Western
,
Cell Division
,
Cell Line, Tumor
,
DNA Primers
,
Doxycycline - pharmacology
,
growth kinetics
,
hypoxia inducible factor β (HIF-1β)
,
Immunohistochemistry
,
Mice
,
Neoplasms, Experimental - physiopathology
,
Reverse Transcriptase Polymerase Chain Reaction
,
tumor
,
xenograft
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