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

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.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Dan C,Zhang H,Zeng W,Huang L,Gong X,Li H,Yang E,Wang L,Yao Q

doi

10.3892/ol.2018.9677

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

1094-1100

issue

1

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-9677

journal_volume

17

pub_type

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