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- W2064001475 abstract "Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLColon cancer is the second most lethal malignancy in the United States. The majority of deaths are related to metastasis, for which no effective therapies are currently available. While much is known about oncogenic initiation of colon cancer, the mechanisms by which cancer cells survive and metastasize in spite of the cellular stresses associated with this process require further investigation. Recent studies indicated that deregulation of apoptosis contributes to metastasis, and deregulation of Bcl-2 family members, which control the mitochondrial-dependent apoptosis pathway, is correlated with cancer progression.We have initiated these studies using a unique othotopic implant model based on closely related colon cancer cell lines. HCT116 and HCT116b cells were isolated from the same primary colon tumor and both bear the H1047R PIK3CA mutation and form progressively growing invasive orthotopic primary tumors. However, only HCT116 cells exhibit metastatic potential. Interestingly, we found that Bcl-2 is highly expressed in HCT116 cells, but not in HCT116b cells. Overexpression of exogenous Bcl-2 in HCT116b cells, and complementary studies by shRNA mediated stable knockdown and overexpression of dominant negative forms of Bcl-2 molecule in metastatic HCT116 cells indicated that Bcl-2 is essential for their ability to withstand external stress. Current studies in our orthotopic model demonstrated that HCT116b tumors bearing exogenous Bcl-2 associated with increased cell survival and reduced center necrosis. Future study will determine whether this significant alteration in the expression of Bcl-2 associates with the distal metastatic capability of colon cancer.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5262. doi:10.1158/1538-7445.AM2011-5262" @default.
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- W2064001475 date "2011-04-15" @default.
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- W2064001475 title "Abstract 5262: The role of Bcl-2 in colon cancer metastatic progression" @default.
- W2064001475 doi "https://doi.org/10.1158/1538-7445.am2011-5262" @default.
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