# Aberrant Activation of Androgen Signaling Pathways in African American Prostate Cancer

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $539,633

## Abstract

Project Summary
 African American (AA) men have an increased risk for both prostate cancer (PCa) incidence and
mortality. Although socio-economic status and other environmental and cultural factors likely contribute to this
racial disparity, emerging evidence has shown an important role of genetic and epigenetic factors in the
pathogenesis of AA PCa.
 Androgens and the androgen receptor (AR)-mediated signaling pathways play a central role in prostate
tumorigenesis. The AR is a ligand-induced transcriptional factor and contains an N-terminal transactivation
domain (NTD). The NTD of human AR possesses polymorphic trinucleotide repeats, CAGs (cytosine, adenine,
guanine), which codes for the polyglutamine (PolyQ) tract. The length of CAG repeats in the human AR gene
has been shown to be inversely correlated with the risk of developing PCa, age of disease onset, and risk of
advanced PCa at diagnosis. Intriguingly, AA men bear shorter CAG repeats significantly more frequently than
Caucasian American (CA) men, linking the length of polyQ tracts to the pathogenesis of PCa in AA men.
Additionally, a significant co-activation of the androgen and Wnt signaling pathways has been revealed in fast
growing and early onset PCa, specifically enriched in AA PCa samples. Moreover, emerging evidence has
shown a niche role of stromal AR to support prostatic epithelial oncogenesis. However, despite these intriguing
findings and past scientific progress, the oncogenic role and related molecular mechanism for AR-mediated
signaling pathways in PCa tumorigenesis, specifically in AA PCa racial disparity, remain elusively. One of the
bottlenecks for these shortfalls is the lack of biologically relevant animal models that can recapitulate aberrant
AR activation in promoting PCa development and progression, mimicking the situation in AA patients. To
directly address this challenge, we propose a series of experiments using our new and relevant animal models,
human PCa samples, single-cell RNA sequencing, and other advanced approaches to directly test our central
hypothesis that aberrant activation of the AR bearing short polyQ tracts in both prostatic epithelia and stroma
promotes PCa initiation, progression, and hormone refractoriness in AA patients. Successful completion of the
proposed study should directly impact the current paradigms and lead to the development of new preventive
and therapeutic strategies to improve clinical outcomes for AA PCa patients.

## Key facts

- **NIH application ID:** 10850752
- **Project number:** 1R01CA288392-01
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** ZIJIE SUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $539,633
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850752

## Citation

> US National Institutes of Health, RePORTER application 10850752, Aberrant Activation of Androgen Signaling Pathways in African American Prostate Cancer (1R01CA288392-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10850752. Licensed CC0.

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