Grants and Contracts Details
Description
"Adenocarcinoma of the prostate is commonly diagnosed in the United States. Prostate cancer (PC) is second
only to lung cancer as a leading cause of male cancer deaths (CDC & NCI). African-Americans (AA) are nearly
1.6 times more likely to be diagnosed with PC than Caucasian-American (CA) men and 2.4 times more likely to
die from the disease. There are known growth-inhibitory roles of glucocorticoid (GC) hormones in PC. However,
eventually, the PC growth becomes refractory to hormone therapy, including anti-androgens, and the disease
“escapes” that is becomes “castrate-resistant” and progresses clinically. This grant proposal seeks to investigate
the GC receptor isoforms (GRα and GRβ) in both normal and malignant prostate epithelial cells. GC responses
are mediated by the major GR isoform, GRα – a hormone-activated transcription factor in the nuclear receptor
family. GRβ inhibits GRα to cause GC resistance, which may cultivate hormone-refractory PC. In the preliminary
data, we show that GRβ is higher in adenocarcinoma compared to normal prostates. We also demonstrate that
GRβ increases migration and androgen-induced growth in human PC cell lines. A primary endpoint will
investigate GRβ and GRα expression in whole prostates removed surgically from AA and CA patients with
known, clinically localized PC. A secondary endpoint will determine how GRβ affects signaling pathways for
growth and transcriptional activity of the androgen receptor (AR). We will characterize the GRβ signaling in
androgen-dependent and -independent cell lines established in my laboratory (vide infra). These proposed
studies will provide the foundation for the hypothesis that GRβ expression increases in prostate cancer patients,
leading to castrate-resistant cell growth refractory to hormone ablation therapy. The research findings may
impact PC treatment by allowing for the development of strategies for rational drug design that may lead to novel
treatments targeting GRβ and provide the basis for studies in the management of prostate cancer."
only to lung cancer as a leading cause of male cancer deaths (CDC & NCI). African-Americans (AA) are nearly
1.6 times more likely to be diagnosed with PC than Caucasian-American (CA) men and 2.4 times more likely to
die from the disease. There are known growth-inhibitory roles of glucocorticoid (GC) hormones in PC. However,
eventually, the PC growth becomes refractory to hormone therapy, including anti-androgens, and the disease
“escapes” that is becomes “castrate-resistant” and progresses clinically. This grant proposal seeks to investigate
the GC receptor isoforms (GRα and GRβ) in both normal and malignant prostate epithelial cells. GC responses
are mediated by the major GR isoform, GRα – a hormone-activated transcription factor in the nuclear receptor
family. GRβ inhibits GRα to cause GC resistance, which may cultivate hormone-refractory PC. In the preliminary
data, we show that GRβ is higher in adenocarcinoma compared to normal prostates. We also demonstrate that
GRβ increases migration and androgen-induced growth in human PC cell lines. A primary endpoint will
investigate GRβ and GRα expression in whole prostates removed surgically from AA and CA patients with
known, clinically localized PC. A secondary endpoint will determine how GRβ affects signaling pathways for
growth and transcriptional activity of the androgen receptor (AR). We will characterize the GRβ signaling in
androgen-dependent and -independent cell lines established in my laboratory (vide infra). These proposed
studies will provide the foundation for the hypothesis that GRβ expression increases in prostate cancer patients,
leading to castrate-resistant cell growth refractory to hormone ablation therapy. The research findings may
impact PC treatment by allowing for the development of strategies for rational drug design that may lead to novel
treatments targeting GRβ and provide the basis for studies in the management of prostate cancer."
| Status | Finished |
|---|---|
| Effective start/end date | 2/1/23 → 1/31/24 |
Funding
- University of Kentucky UNITE Research Priority Area: $25,000.00
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