Altered localization of a coactivator sensitizes breast cancer cells to tumor necrosis factor-induced apoptosis

Molecular Cancer Therapeutics
Suresh K RayalaRakesh Kumar

Abstract

Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1) is a novel coregulator of the estrogen receptor that plays a role in both genomic and nongenomic actions of the estrogen receptor. Emerging studies suggest that in addition to the nuclear localization of PELP1, it is predominantly localized in the cytoplasm in human breast tumors, leading to excessive nongenomic signaling and possibly to tamoxifen resistance. The mechanisms underlying resistance to hormones in preclinical model systems remain under intense investigation. In an effort to develop a model system to treat tumor cells with cytoplasmic PELP1 expression and tamoxifen resistance, here we used the cytokine tumor necrosis factor (TNF)-alpha. We found that clones of MCF-7 human breast cancer cells overexpressing PELP1 in the cytoplasm were distinctly sensitive to TNF-alpha-induced apoptosis than were wild-type nuclear PELP1- and pcDNA vector-expressing clones as revealed by cell growth assay, cell cycle analysis, Annexin V staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. We also found that the clones with cytoplasmic PELP1 overexpression had significantly less antiapoptotic protein Bcl-2 and nuclear factor-kappaB DNA bin...Continue Reading

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Citations

Jul 11, 2006·Clinical & Experimental Metastasis·Rajib Rajhans, Ratna K Vadlamudi
Apr 24, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Jianhua HuangQiao Li
Dec 17, 2009·IUBMB Life·Dimple ChakravartyRatna K Vadlamudi
Aug 13, 2013·Molecular and Cellular Endocrinology·Brian J GirardJulie H Ostrander
May 26, 2007·Nuclear Receptor Signaling·Ratna K Vadlamudi, Rakesh Kumar
May 11, 2006·The Journal of Biological Chemistry·Suresh K RayalaRakesh Kumar
Jul 15, 2015·Molecular Endocrinology·Preethi RavindranathanGanesh V Raj

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