Abstract 1594: Transgenic overexpression of NanogP8 in the mouse prostate does not initiate tumorigenesis nor promotes tumor development in the Hi-Myc mouse model

Abstract

Abstract Nanog1 is a homeobox transcription factor critical for the self-renewal and pluripotency of ES cells. NanogP8 is a retrotransposed homolog of Nanog1 preferentially expressed in somatic cancer cells. Work from our lab has shown that shRNA-mediated knockdown of NanogP8 in prostate, breast, and colon cancer cells inhibits tumor regeneration whereas inducible overexpression of NanogP8 in somatic cancer cells promotes cancer stem cell phenotypes and properties. A key unanswered question is whether tissue-specific overexpression of NanogP8 is sufficient to promote tumor development in vivo. To address this question, we generated a NanogP8 transgenic mouse model in which the NanogP8 cDNA derived from a primary prostate cancer was driven by the ARR2Pb promoter to direct prostate-specific expression. IHC analysis revealed that human NanogP8 was expressed mainly in the mouse prostate and the expression levels varied from lobe to lobe, with the highest expression in the lateral and ventral lobes. The ARR2Pb-NanogP8 transgenic mice were viable, developed normally, and did not form spontaneous tumors during the observation period of >2 years. In addition, both wild-type and ARR2Pb-NanogP8 transgenic prostates responded similarly to castration and regeneration and did not develop any tumors. These results indicate that overexpression of human NanogP8 in the mouse prostate is insufficient to initiate tumorigenesis in both androgen intact and deprived conditions. We then crossed the ARR2Pb-NanogP8 transgenic mice with ARR2Pb-Myc (i.e., Hi-Myc) mice and found that the double transgenic (i.e., ARR2Pb-NanogP8; Hi-Myc) mice showed similar tumor incidence and histology to the Hi-Myc mice. Unexpectedly, we found white dots in the ventral lobes of the double transgenic mice, which are currently being characterized. Taken together, our present work demonstrates that transgenic overexpression of NanogP8 in the mouse prostate does not initiate tumorigenesis nor promotes tumor development in the Hi-Myc mouse model. These results are consistent with our recent findings that NanogP8 overexpression fails to initiate tumorigenesis in a K14-NanogP8 transgenic model. Our results are also consistent with others' recent work showing that NanogP8 overexpression in transgenic animals is insufficient to initiate mammary tumor development. Citation Format: Shuai Gong, Bigang Liu. Transgenic overexpression of NanogP8 in the mouse prostate does not initiate tumorigenesis nor promotes tumor development in the Hi-Myc mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1594. doi:10.1158/1538-7445.AM2014-1594