# Study the Mechanism of Retinoblastoma Protein Mediated Androgen Receptor Transcriptional Repression Activity on DNA Replication

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS BOSTON · 2020 · $348,844

## Abstract

Project Summary
 While AR has been extensively characterized as a transcriptional activator, it was recently reported to
function as a transcriptional repressor to suppress a subset of genes. Significantly, through AR ChIP-seq and
transcriptome profiling in prostate cancer cells we have found that the directly AR-repressed genes are highly
enriched for DNA replication function and majority of those genes were consistently increased in CRPC clinical
samples. We then discovered that this direct transcriptional repression activity of AR was mediated by
androgen-stimulated recruitment of hypophosphorylated Rb. Androgens is also known to stimulate growth by
further AR transcriptional activation of genes driving lipid and sterol synthesis, and other metabolic functions,
with subsequent cyclin dependent kinase activation and Rb hyperphosphorylation. Overexpression of AR in
prostate cancer cells could overcome this growth stimulatory effect. These findings demonstrate that AR has
an Rb-dependent anti-proliferative function, which may be compromised in CRPC cells with Rb-deficiency and
could be enhanced by blocking Rb phosphorylation. The objective of this proposal is to determine the function
roles of AR recruitment of Rb in regulating transcription of DNA replication genes and cell cycle progression of
PCa tumor cells (specific aim 1), to determine the molecular basis for AR interaction with hypophosphorylated
Rb and characterize the distinct Rb complex recruited by AR to the suppression sits (specific aim 2), and to
conduct a genome wide analysis to identify Rb dependent AR suppression sites and determine the mechanism
of actions and function roles of these sites in prostate cancer cells (specific aim 3).

## Key facts

- **NIH application ID:** 9994239
- **Project number:** 5R01CA211350-04
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS BOSTON
- **Principal Investigator:** Changmeng Cai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,844
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994239

## Citation

> US National Institutes of Health, RePORTER application 9994239, Study the Mechanism of Retinoblastoma Protein Mediated Androgen Receptor Transcriptional Repression Activity on DNA Replication (5R01CA211350-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994239. Licensed CC0.

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