Oncotarget

Research Papers:

The essential role of GATA transcription factors in adult murine prostate

Lijuan Xiao, Qin Feng, Zheng Zhang, Fen Wang, John P. Lydon, Michael M. Ittmann, Li Xin, Nicholas Mitsiades and Bin He _

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Oncotarget. 2016; 7:47891-47903. https://doi.org/10.18632/oncotarget.10294

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Abstract

Lijuan Xiao1, Qin Feng2, Zheng Zhang2, Fen Wang3, John P. Lydon2, Michael M. Ittmann4,5, Li Xin2, Nicholas Mitsiades1,2, Bin He1,2

1Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX, USA

2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

3The Center for Cancer and Stem Cell Biology, Institute of Bioscience and Technology, Texas A&M Health Science Center, Houston, TX, USA

4Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

5Michael E. DeBakey Veterans Affairs Medical Center, US Department of Veterans Affairs, Houston, TX, USA

Correspondence to:

Bin He, email: bh[email protected]

Nicholas Mitsiades, email: [email protected]

Keywords: GATA2, GATA3, FoxA1, androgen receptor, prostate cancer

Received: April 18, 2016     Accepted: May 17, 2016     Published: June 25, 2016

ABSTRACT

GATA transcription factors are essential in mammalian cell lineage determination and have a critical role in cancer development. In cultured prostate cancer cells, GATA2 coordinates with androgen receptor (AR) to regulate gene transcription. In the murine prostate, among six GATA members, GATA2 and GATA3 are expressed. Immunofluorescence staining revealed that both GATA factors predominantly localize in the nuclei of luminal epithelial cells. The pioneer factor FoxA1 is exclusively detected in the luminal cells, whereas AR is detected in both luminal and basal cells. Using genetic engineering, we generated prostate-specific GATA2 and GATA3 knockout (KO) mice. Ablation of single GATA gene had marginal effect on prostate morphology and AR target gene expression, likely due to their genetic compensation. Double KO mice exhibited PIN III to IV lesions, but decreased prostate to body weight ratio, altered AR target gene expression, and expansion of p63-positive basal cells. However, deletion of GATA2 and GATA3 did not reduce the mRNA or protein levels of AR or FoxA1, indicating that GATA factors are not required for AR or FoxA1 expression in adult prostate. Surprisingly, GATA2 and GATA3 exhibit minimal expression in the ventral prostatic (VP) lobe. In contrast, FoxA1 and AR expression levels in VP are at least as high as those in anterior prostatic (AP) and dorsal-lateral prostatic (DLP) lobes. Together, our results indicate that GATA2 and GATA3 are essential for adult murine prostate function and in vivo AR signaling, and the lack of the GATA factor expression in the VP suggests a fundamental difference between VP and other prostatic lobes.


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