Oncotarget

Research Papers:

Transgenic overexpression of NanogP8 in the mouse prostate is insufficient to initiate tumorigenesis but weakly promotes tumor development in the Hi-Myc mouse model

Bigang Liu, Shuai Gong, Qiuhui Li, Xin Chen, John Moore, Mahipal V. Suraneni, Mark D. Badeaux, Collene R. Jeter, Jianjun Shen, Rashid Mehmood, Qingxia Fan and Dean G. Tang _

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Oncotarget. 2017; 8:52746-52760. https://doi.org/10.18632/oncotarget.17186

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Abstract

Bigang Liu1,*, Shuai Gong1,2,*, Qiuhui Li1,3, Xin Chen1,3, John Moore1, Mahipal V. Suraneni1, Mark D. Badeaux1, Collene R. Jeter1, Jianjun Shen1, Rashid Mehmood3, Qingxia Fan2 and Dean G. Tang1,3,4

1Department of Molecular Carcinogenesis, University of Texas M.D Anderson Cancer Center, Science Park, Smithville, TX 78957, USA

2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China

3Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

4Cancer Stem Cell Institute, Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

*These authors have contributed equally to this work

Correspondence to:

Dean G. Tang, email: Dean.Tang@Roswellpark.org

Keywords: NanogP8, Nanog, prostate, prostate cancer, stem cells

Received: February 13, 2017    Accepted: March 21, 2017    Published: April 18, 2017

ABSTRACT

This project was undertaken to address a critical cancer biology question: Is overexpression of the pluripotency molecule Nanog sufficient to initiate tumor development in a somatic tissue? Nanog1 is critical for the self-renewal and pluripotency of ES cells, and its retrotransposed homolog, NanogP8 is preferentially expressed in somatic cancer cells. Our work has shown that shRNA-mediated knockdown of NanogP8 in prostate, breast, and colon cancer cells inhibits tumor regeneration whereas inducible overexpression of NanogP8 promotes cancer stem cell phenotypes and properties. To address the key unanswered question whether tissue-specific overexpression of NanogP8 is sufficient to promote tumor development in vivo, we generated a NanogP8 transgenic mouse model, in which the ARR2PB promoter was used to drive NanogP8 cDNA. Surprisingly, the ARR2PB-NanogP8 transgenic mice were viable, developed normally, and did not form spontaneous tumors in >2 years. Also, both wild type and ARR2PB-NanogP8 transgenic mice responded similarly to castration and regeneration and castrated ARR2PB-NanogP8 transgenic mice also did not develop tumors. By crossing the ARR2PB-NanogP8 transgenic mice with ARR2PB-Myc (i.e., Hi-Myc) mice, we found that the double transgenic (i.e., ARR2PB-NanogP8; Hi-Myc) mice showed similar tumor incidence and histology to the Hi-Myc mice. Interestingly, however, we observed white dots in the ventral lobes of the double transgenic prostates, which were characterized as overgrown ductules/buds featured by crowded atypical Nanog-expressing luminal cells. Taken together, our present work demonstrates that transgenic overexpression of NanogP8 in the mouse prostate is insufficient to initiate tumorigenesis but weakly promotes tumor development in the Hi-Myc mouse model.


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