# The role of autophagy in cadmium induced prostate carcinogenesis

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $383,328

## Abstract

Project Summary
It has been clearly demonstrated that exposure to the environmental toxicant cadmium is associated
with a variety of human diseases including prostate cancer. Prostate cancer is the second leading cause
of cancer death in United States. Although an association has been established, the mechanism by
which this metal induces cellular transformation has yet to be defined. One underexplored process that
may be affected by cadmium is oncogenic autophagy, a process that promotes cancer cell survival. Our
preliminary data clearly shows that chronic exposure to cadmium leads to cellular transformation and
that this transformation occurs via autophagy through changes in Placenta Specific 8 (Plac8) expression.
Additionally, Plac8 is observed in human prostate cancer, but not in benign prostatic hyperplasia tissues.
Based on our preliminary results we hypothesize that cadmium-induced cellular transformation is
mediated by the induction of autophagy and that Plac8 is an essential regulator of this process.
We will test this hypothesis using a combination of approaches in normal prostate epithelial (RWPE-1),
transforming cells and cadmium-transformed prostate epithelial (CTPE) cells, mice and human prostate
cancer. The goals of this project are to explore an innovative model for the regulation of autophagy by
cadmium; where short term metal exposure induces the apoptosis, while chronic low dose exposure,
which more accurately represents human etiology of cadmium toxicity; autophagy acts oncogenic
leading to transformation. The interaction between cadmium, autophagy/apoptosis and Plac8
expression will be defined using three approaches: Specific Aim 1: Establish the mechanistic relationship
between cadmium exposure and the induction of autophagy in prostate epithelial cells. Specific Aim 2:
Determine the mechanism by-which cadmium induces Plac8 expression to regulate pro-survival
signaling autophagy. Specific Aim -3: Determine the oncogenic role of Plac8 in vivo. The successful
completion of these goals represents the first studies on the role of autophagy/Plac8 in cadmium-
induced prostate cancer. It will also inform on the applicability of using Plac8 as a prostate cancer
biomarker and of targeting this protein to inhibit metal-induced prostate cancer.

## Key facts

- **NIH application ID:** 9830071
- **Project number:** 5R01ES028102-03
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Chendil Damodaran
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,328
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830071

## Citation

> US National Institutes of Health, RePORTER application 9830071, The role of autophagy in cadmium induced prostate carcinogenesis (5R01ES028102-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830071. Licensed CC0.

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