# Impact of Cox‐2 on estrogen receptor beta action in prostate epithelial cells

> **NIH NIH U54** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $218,320

## Abstract

Project Summary:
Prostatic inflammation is a common feature of symptomatic benign prostatic hyperplasia (BPH) and may alter
epithelial cell proliferation and tissue homeostasis in BPH through cytokine induction of proinflammatory
signaling mediators such as cyclooxygenase-2 (Cox-2). Cox-2 is overexpressed in luminal epithelial cells of
BPH tissue but predominantly in regions of chronic inflammation. One clinical trial reported only a short-term
benefit of a Cox-2 inhibitor (i.e. nonsteroidal anti-inflammatory agents [NSAIDs] such as rofecoxib) in reducing
LUTS symptoms when combined with a 5AR inhibitor. The mechanism responsible for the limited clinical
effectiveness of Cox-2 inhibition is not known. In the human BPH-1 prostate epithelial cell line (which
expresses high basal levels of Cox-2), pharmacologic or molecular ablation of Cox-2 expression limits the
protective effects of ERß through selective disruptions in steroidogenic enzyme expression leading to a
reduced production of ERß ligands from testosterone. We therefore hypothesize that the limited effectiveness
of NSAIDs in current BPH clinical trials is due to disruptions in prostatic steroidogenic pathways that generate
ligands for the tissue protective ERß. Four Aims are proposed to test this hypothesis: Aim 1 will determine the
impact of Cox-2 on ERß ligand production in PrECs. Aim 2 will identify genome-wide basal and ERß-regulated
gene expression patterns influenced by acute or long-term adaptive responses to Cox-2 overexpression in
PrECs. Aim 3 will identify the impact of Cox-2 and ERß on targets relevant to polarized epithelial cell function
in 3- dimensional cultures of PrECs and ERß knockout mice. Aim 4 will determine the impact of Cox-2 on ERß
signaling in human prostate explants and a rodent model of prostatic inflammation

## Key facts

- **NIH application ID:** 10002345
- **Project number:** 5U54DK112079-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Donald B DeFranco
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,320
- **Award type:** 5
- **Project period:** 2016-09-22 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002345

## Citation

> US National Institutes of Health, RePORTER application 10002345, Impact of Cox‐2 on estrogen receptor beta action in prostate epithelial cells (5U54DK112079-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10002345. Licensed CC0.

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