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Nonapoptotic Function of Caspase-6 in Promoting Mammary Carcinogenesis

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Final rept. 15 Sep 2010-14 Dec 2011

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Malignancy is defined as the elevated mobility and invasiveness of tumor cells, and a deformed nuclear morphology is a common feature of malignant cells. We hypothesized that the decrease or absence of nesprin-1 in breast cancer cells may account for the malignant features of the neoplastic cells, the deformed nuclear morphology and invasivenesshigh motility. We propose a pilot study to test this hypothesis. Indeed, we found that nesprin-1 expression is commonly lost in malignant breast cancer cell lines Aim 1. We found that the suppression of nesprin-1 by siRNA led to nuclear morphological deformation and increased invasion Aim 2. We also tested restoration of nesprin-1 expression in malignant breast cancer cells and nesprin-1 was not sufficiently stable to produce other significant phenotypes in the transfected cells, likely due to technical limitation Aim 3. The results of these pilot experiments support the initial hypothesis of nesprin-1 as a metastatic suppressor gene and as an underlying link between two prominent features of a malignant cell, nuclear deformation and cellular malleability. We also realize further complexity of nesprin-1 function in breast cancer suppression. The pilot study promotes us to seek further investigation into the role of nesprin-1 in cancer malignancy.

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  • Medicine and Medical Research

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