# CAPER, a New Regulator of DNA Damage and Repair in Triple Negative Breast Cancer

> **NIH NIH R15** · SAINT JOSEPH'S UNIVERSITY · 2022 · $434,998

## Abstract

ABSTRACT
Triple negative breast cancer (TNBC) has the poorest clinical outcome amongst all breast cancer subtypes.
TNBC lacks the expression of the three major receptors found in other subtypes (estrogen receptor [ER],
progesterone receptor, and/or hormone epidermal growth factor receptor-2) making this cancer particularly
challenging with regards to treatment modalities. Novel targeted treatments that could kill TNBC cells or sensitize
them to chemo- and radiation therapies are highly coveted to increase survival of these patients. Due to its fast
proliferative rate, TNBC relies heavily on DNA repair mechanisms for its survival and proteins involved in this
important checkpoint are attractive targets for cancer treatment. CAPER (Rbm39) protein was recently shown to
be overexpressed in breast cancer specimens compared to normal breast tissues. While CAPER knockdown
inhibits breast cancer cell growth, its role on DNA damage and repair mechanisms in breast cancer and its role
in TNBC progression and response to chemo- and radiation therapies remain completely unexplored. Our
preliminary data demonstrate that knockdown of CAPER expression in TNBC cells increases DNA damage as
reflected by increased phosphorylation of H2AX and ATM. The decreased total cell number and increased
caspase-3/7 cleavage observed following CAPER knockdown in MDA-MB-231 and BT549 TNBC cells is
suggestive of insurmountable DNA damage leading to programmed cell death (apoptosis). The effect of CAPER
knockdown on DNA damage in TNBC cells was cell cycle-independent and selective to cancer cells, as non-
tumorigenic cells lack the expression of CAPER and remain unaffected following delivery of lentiviral CAPER
shRNAs. Our preliminary results also revealed that DNA repair proteins RAD-51, C-Alb and RB were significantly
downregulated in TNBC following CAPER knockdown. We posit that CAPER overexpression in TNBC plays an
important role in protection against DNA damage by optimizing DNA repair pathways. The current proposal
builds on our previous work and preliminary results and aims to delineate the roles of CAPER in basal DNA
damage/repair pathways and to determine its clinical relevance in TNBC growth using both immunocompromised
(xenograft) and immunocompetent (syngeneic) orthotopic mouse models (Aim 1). Importantly, we will also use
these TNBC cells and mouse models to test the unexplored role of CAPER in the response to DNA damaging
chemo- and radiation therapies in both in vitro and in vivo settings (Aim 2). The current proposal will validate the
role of CAPER as an important signaling molecule in the progression of TNBC as well as response to DNA
damage using clinically relevant models that also incorporate immune surveillance and will be insightful in the
further development of targeted therapies for the treatment of TNBC.

## Key facts

- **NIH application ID:** 10359895
- **Project number:** 1R15CA242344-01A1
- **Recipient organization:** SAINT JOSEPH'S UNIVERSITY
- **Principal Investigator:** Jean-Francois Jasmin
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $434,998
- **Award type:** 1
- **Project period:** 2022-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359895

## Citation

> US National Institutes of Health, RePORTER application 10359895, CAPER, a New Regulator of DNA Damage and Repair in Triple Negative Breast Cancer (1R15CA242344-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10359895. Licensed CC0.

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