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- W2051825462 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCOne general characteristic of fast-growing solid tumors including breast cancer is the development of intratumoral hypoxia. The activation of hypoxia-inducible factor-1α (HIF-1α) by intratumoral hypoxia stimulates a group of downstream genes including vascular endothelial growth factor (VEGF) that are responsible for tumor malignant progression. Loss of p16 expression occurs in many cancers including breast cancer. Our studies showed that, by ectopic expression via adenoviral-mediated gene transfer, p16 downregulates VEGF gene expression by neutralizing the transactivation of HIF-1α, and suppresses breast cancer angiogenesis and metastasis. To investigate whether p16 directly affects one or more aspects of the metastatic cascade, MDA-MB-231 cells infected with lentivirus expressing Tet-on inducible p16 were used to study the p16 effects on growth, adhesion and migration of the breast cancer cells. We found that p16 inhibits MDA-MB-231 cell proliferation (45.6% inhibition) and hypoxia-induced cell migration (36% inhibition), but has no apparent effect on cell adhesion. The p16-mediated inhibition of hypoxia-induced cell migration parallels with p16’s inhibition of HIF-1α transactivation activity. These results indicate that p16’s ability to suppress breast tumor metastasis may result from a combined p16-mediated actions including inhibition of cell proliferation, migration, and angiogenesis. This study suggests that p16 gene therapy may have clinical potentials to treat breast cancer due to p16’s multiple-level anti-cancer capabilities: inhibiting proliferation, inducing apoptosis, blocking tumor angiogenesis, inhibiting cell migration and suppressing metastasis.Citation Format: Yi Lu. Blocking hypoxia-induced tumor cell migration by p16/INK4A. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3864. doi:10.1158/1538-7445.AM2013-3864" @default.
- W2051825462 created "2016-06-24" @default.
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- W2051825462 date "2013-04-15" @default.
- W2051825462 modified "2023-09-27" @default.
- W2051825462 title "Abstract 3864: Blocking hypoxia-induced tumor cell migration by p16/INK4A." @default.
- W2051825462 doi "https://doi.org/10.1158/1538-7445.am2013-3864" @default.
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