HNF1B expression regulates ECI2 gene expression, potentially serving a role in prostate cancer progression

Dan,Chao; Zhang,Haiyan; Zeng,Wenjing; Huang,Li; Gong,Xiaoxin; Li,Hao; Yang,Erjiang; Wang,Li; Yao,Qisheng

doi:10.3892/ol.2018.9677

HNF1B expression regulates ECI2 gene expression, potentially serving a role in prostate cancer progression

Authors:
- Chao Dan
- Haiyan Zhang
- Wenjing Zeng
- Li Huang
- Xiaoxin Gong
- Hao Li
- Erjiang Yang
- Li Wang
- Qisheng Yao
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Affiliations: Department of Urology and Andrology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Blood Transfusion, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: November 8, 2018 https://doi.org/10.3892/ol.2018.9677
Pages: 1094-1100
Copyright: © Dan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer is the most common form of cancer in men, with increased incidence rates observed in older individuals. Prostate cancer is primarily driven via activation of the androgen receptor (AR), the principal transcriptional factor governing prostate cancer cellular programming and its associated metabolism. One of the downstream targets of AR is hepatocyte nuclear factor‑1β (HNF1B), an important oncogenic transcription factor in prostate cancer. In the present study, the regulatory role of HNF1B in enoyl‑CoA‑(Δ) isomerase 2 (ECI2) expression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model was investigated. Using this model, tumor progression and associated pathological alterations at 12, 18 and 24 weeks were analyzed. Histological sectioning revealed pathological alterations over time, including thickening of glandular epithelial cells (12 weeks), increases in cellular proliferation (18 weeks), and extensive thickening and hardening of the tissue layer (24 weeks). Expression levels of HNF1B and ECI2 proteins were validated by immunohistochemistry and western blotting at different stages of prostate cancer development. HNF1B and ECI2 exhibited minimal differences in protein expression at 12 weeks in TRAMP+ mice. However, by 18 weeks, TRAMP+ mice exhibited multi‑fold increases in HNF1B expression levels, along with downregulation of ECI2. These effects were reversed at 24 weeks, indicating an important time‑dependent regulation of gene expression. Taken together, these results demonstrated that upon tumor progression, the initial tumor‑protective effect of HNF1B is lost along with downregulated expression of HNF1B and increased expression of ECI2.

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