The Role of Glucocorticoid Signaling in Prostate Cancer Health Disparities

<p>African-American men are more likely to develop aggressive prostate cancer (PCa) and die from the disease than other ethnic groups. Glucocorticoid signaling is a contributing biological factor to worse PCa prognosis, and is emerging as a key driver of PCa progression in the absence of androgens. The mechanism involves glucocorticoids binding to glucocorticoid receptor (GR) and bypassing the androgen receptor (AR) signaling pathway to activate AR-target genes that promote tumor aggressiveness and therapy-resistance. This is problematic as African-American men have hypersensitive GR signaling and chronically-elevated levels of glucocorticoids linked to cumulative stressful life events. To explore the role of glucocorticoid signaling in PCa health disparities, this dissertation used a racially diverse pre-clinical model to examine the effects of GR activation on the expression of stress oncoproteins linked to tumor aggressiveness and therapy-resistance, specifically Lens Epithelium-Derived Growth Factor p75 (LEDGF/p75) and Clusterin (CLU). Results revealed a robust pattern of GR-induced upregulation of LEDGF/p75 and CLU in African-American (AA) PCa cells compared to European-American (EA) PCa cells. We also detected increased GR transcript expression in AA PCa tissues, compared to EA tissues, using Oncomine microarray datasets. In addition, a trend towards elevated circulating LEDGF/p75 and CLU was observed in sera of AA patient samples. Taken together, these findings provide an initial framework for understanding the contribution of GR signaling to PCa health disparities.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Basic Sciences

Year

2018

Author dc:creator

• Burnham, Leanne W.

Contributors dc:contributor

• Casiano, Carlos A.
• Figueroa, Johnny D.
• Mata-Greenwood, Eugenia
• Montgomery, Susanne B.
• Wilson, Colwick
• Zhang, lubo

• Medical Physiology
• Medical Sciences
• Neoplasms
• Race and Ethnicity
• Social Work
• Glucocorticoids -- Physiology; Prostatic Neoplasms; Prostate Cancer; African Americans
• Glucocorticoid Signaling
• Health Disparities

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/525

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1524