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Tumor Biology

Abstract 4989: Conditional NFAT activation promotes prostate oncogenesis through cell autonomous and non-cell autonomous effects.

Kalyan Reddy Manda, Piyush Tripathi, Yinqiu Wang, Peter A. Humphrey, Minggui Pan and Feng Chen
Kalyan Reddy Manda
1Washington University School of Medicine, St Louis, MO;
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Piyush Tripathi
1Washington University School of Medicine, St Louis, MO;
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Yinqiu Wang
1Washington University School of Medicine, St Louis, MO;
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Peter A. Humphrey
1Washington University School of Medicine, St Louis, MO;
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Minggui Pan
2Kaiser Permanente Medical Center, Santa Clara, CA.
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Feng Chen
1Washington University School of Medicine, St Louis, MO;
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DOI: 10.1158/1538-7445.AM2013-4989 Published April 2013
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Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Abstract

Although the activation of nuclear factor of activated T Cells (NFAT) has been linked to cellular transformation and its upregulation has been found in multiple tumor types, its potential role in prostate cancer (PCa) is unknown. We have recently found that NFATc1 activation in prostate epithelium results in prostatic intraepithelial neoplasia (PIN) that progresses to prostate adenocarcinoma in a Doxycycline (Dox)-inducible murine model. The adenocarcinoma primarily consists of Cytokeratin 8 (CK8)+, Androgen receptor (AR)+ luminal epithelial cells and reactive stroma with features similar to the most common types of human PCa. Both cells with NFATc1 activation and neighboring cells without NFATc1 activation have significant upregulation of c-Myc and activation of Stat3. Besides known and suspected NFATc1 targets, such as Spp1, we have revealed the early upregulation of a number of cytokines and cytokine receptors, as key molecular components of an inflammatory and pro-mitogenic microenvironment that promotes both NFATc1+ and NFATc1− cells to participate in tumor formation. Thus, NFATc1 activation has cell autonomous effects on the NFATc1+ cells and non-cell autonomous effects on neighboring cells through secreted factors, resulting in eciprocal prostatic epithelial-stromal interactions for promoting PCa development. Our studies present the first direct in vivo evidence that NFATc1 activation can induce PCa resembling human PCa and provide a versatile platform to further study the pathogenic mechanism of PCa.

Citation Format: Kalyan Reddy Manda, Piyush Tripathi, Yinqiu Wang, Peter A. Humphrey, Minggui Pan, Feng Chen. Conditional NFAT activation promotes prostate oncogenesis through cell autonomous and non-cell autonomous effects. [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 4989. doi:10.1158/1538-7445.AM2013-4989

  • ©2013 American Association for Cancer Research
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Cancer Research: 73 (8 Supplement)
April 2013
Volume 73, Issue 8 Supplement
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Abstract 4989: Conditional NFAT activation promotes prostate oncogenesis through cell autonomous and non-cell autonomous effects.
Kalyan Reddy Manda, Piyush Tripathi, Yinqiu Wang, Peter A. Humphrey, Minggui Pan and Feng Chen
Cancer Res April 15 2013 (73) (8 Supplement) 4989; DOI: 10.1158/1538-7445.AM2013-4989

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Abstract 4989: Conditional NFAT activation promotes prostate oncogenesis through cell autonomous and non-cell autonomous effects.
Kalyan Reddy Manda, Piyush Tripathi, Yinqiu Wang, Peter A. Humphrey, Minggui Pan and Feng Chen
Cancer Res April 15 2013 (73) (8 Supplement) 4989; DOI: 10.1158/1538-7445.AM2013-4989
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Cancer Research Online ISSN: 1538-7445
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