# Androgen Signaling in CaP with loss of MAP3K7 and CHD1

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $384,104

## Abstract

Prostate cancer is characterized by large genomic rearrangements and deletions. We show that the genes
CHD1 and MAP3K7 are co-deleted in ERG translocation negative prostate cancer. To demonstrate a
functional cooperativity we used a novel mouse prostate stem cell developmental model and showed that
collaborative loss of CHD1 and MAP3K7 promotes an aggressive prostate cancer phenotype with altered
lineage differentiation, abnormal secretory products, massive nuclear atypia, loss of E-cadherin and
enrichment in neuronal and neuroendocrine markers. Profound alterations in AR expression were also
observed. Using multiple human cell line models we also demonstrate that loss of CHD1 and MAP3K7
promotes castrate-resistant prostate cancer. This project will evaluate downstream targets of AR altered in
tumors with loss of MAP3K7 and CHD1 using functional genomics in vitro and in animal models and assess
the clinical impact of these targets on patient outcome. This work could have impact on the management of the
most aggressive prostate cancer. Co-deletion of CHD1 and MAP3K7 occurs in 10-15 % of primary tumors.
Relapse occurs in approximately 50% of patients with co-deletion. If these deletions occur in primary tumors
and predict poor survival, men could be stratified based on MAP3K7 and CHD1 status. A functional
understanding of this variant of prostate cancer could lead to novel therapeutic targeting strategies in the future.

## Key facts

- **NIH application ID:** 10657393
- **Project number:** 5R01CA262279-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Scott D Cramer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $384,104
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657393

## Citation

> US National Institutes of Health, RePORTER application 10657393, Androgen Signaling in CaP with loss of MAP3K7 and CHD1 (5R01CA262279-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10657393. Licensed CC0.

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