# SerpinA6 Involvement in Prostate Cancer

> **NIH NIH R03** · UNIVERSITY OF FLORIDA · 2020 · $76,250

## Abstract

PROJECT SUMMARY
Study will determine the potential role of SerpinA6 (Corticosteroid-Binding Globulin; a carrier of glucocorticoids
in the plasma) in prostate cancer progression. In castrate resistant prostate cancer (CRPC) patients, presence
of higher levels of IL-6 has been observed. Our preliminary data on CRPC prostate cancer cells represented
decreasing SerpinA6 levels after IL-6 dose response treatment. Circulatory levels of SerpinA6 believed to keep
the steroids inactive and regulate the amount of free hormone acting on target tissues. SerpinA6 contains a
single binding site for glucocorticoid (GC) and progesterone, and both binds (80–90%) to SerpinA6 with high
affinity. Active role of SerpinA6 is in bioavailability of GC for the glucocorticoid receptor, local delivery, and/or
cellular signal transduction of GCs, only the unbound (free) fraction of GCs are biologically active. Moreover
reports suggest that SerpinA6 promoter is transcriptionally regulated via the glucocorticoid receptor (GR), this
suggest that GR has significant role in SerpinA6 regulation. Increasing GR levels in prostate and increasing IL-
6 level in prostate (due to castration) decreases SerpinA6 expression. Evidence in castrate resistant prostate
cancer (CRPC) patients suggests, GR compensates for the lack of androgen receptor (AR) activity in prostate
cancer patients. Additionally reports suggest GR has significant role in prostate cancer cells survival and cell
cycle regulation. Encouraging preliminary data suggest AR and GR directly or indirectly linked with
transcription factor FOXO3a in regulation. We observed increase IL-6 levels in CRPC prostate cancer cells
decrease FOXO3a expression. Goal of this research project is to determine the role of SerpinA6 in progression
of prostate cancer. Therefore, increased GCs in CRPC patients due to inappropriate SerpinA6 level would
increase GR expression in the prostate tissue, which will promote cell survival and proliferation. The proposed
mechanistic study, in in-vitro and in-vivo model system will determine whether decrease SerpinA6 levels in
CRPC cells have potential to promote prostate cancer progression.
Our long term goal is to develop SerpinA6 as potential target for prostate cancer progression, and to
determine SerpinA6 modulation as a therapeutic target to inhibit prostate cancer progression.
Public Health Significance: There is an immediate need for an effective and clinically relevant target, which
has potential role in CRPC progression. We need to have specific and selective targets for progressive events
and also need to have the therapeutic approaches to modulate these targets and prevent the further
progression of prostate cancer.

## Key facts

- **NIH application ID:** 9904589
- **Project number:** 7R03CA230299-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Sanjeev Shukla
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,250
- **Award type:** 7
- **Project period:** 2019-04-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904589

## Citation

> US National Institutes of Health, RePORTER application 9904589, SerpinA6 Involvement in Prostate Cancer (7R03CA230299-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9904589. Licensed CC0.

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