Aryl hydrocarbon nuclear translocator (hypoxia inducible factor 1beta) activity is required more during early than late tumor growth.
Aryl hydrocarbon nuclear translocator (hypoxia inducible factor 1beta) activity is required more during early than late tumor growth.
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DOI：
10.1002/mc.20585
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发表时间：
2010-02
影响因子：
4.6
通讯作者：
Hankinson, O.
中科院分区：
文献类型：
--
作者：
Shi, S.;Yoon, D. Y.;Hodge-Bell, K.;Huerta-Yepez, S.;Hankinson, O.
关键词：
c4 is a derivative of the mouse hepatoma cell line, Hepa-1, that harbors a mutation in the Aryl Hydrocarbon Receptor Nuclear Translocater 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 day 14 and day 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 measureable 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 interactions(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.
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DOI：
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