# Role of High Mobility Group A2 (HMGA2) in Prostate Cancer

> **NIH NIH U54** · CLARK ATLANTA UNIVERSITY · 2021 · $210,732

## Abstract

Project Summary
Black men which includes African American men (AA), Caribbean and African men suffer disproportionately
from prostate cancer and have higher mortality rates as compared to Caucasian men (CA), presenting with
more aggressive disease at the time of diagnosis. Most men who die of prostate cancer present with hormone
refractory and bone metastatic disease. High mobility group protein A2 (HMGA2) belongs to the high mobility
chromosomal proteins that rearrange chromatin and is increased in various cancers. A truncated isoform of
HMGA2 can also be generated by chromosomal rearrangements or alternative splicing. Additionally, HMGA2
single nucleotide polymorphism (SNP) rs1042725 has been associated with variation in bone mineral density,
where the ‘CC’ genotype (more common in Black men vs CA) is associated with higher bone density as
compared to ‘TT’ genotype that is more common in CA. Previously it has been shown that increased bone
density is associated with prostate cancer incidence in older men from Trinidad and Tobago, and it is well
known that Black men have higher bone density than any other race; however it has not been studied with
regards to prostate cancer metastasis. Moreover, HMGA2 SNP rs1042725 has been associated with the
incidence of cervical cancer, but has not been studied with respect to prostate cancer. We have preliminary
data that HMGA2 expression increases with prostate cancer progression and metastasis in patient tissue.
Additionally, we found that overexpression of full-length (wild-type) HMGA2 in LNCaP cells promoted nuclear
expression of HMGA2 and epithelial mesenchymal transition (EMT), while truncated HMGA2 overexpression
led to cytoplasmic localization of HMGA2, increased cell migration via increased Jun-D and reactive oxygen
species (ROS). Finally, culturing less aggressive LNCaP cells with conditioned media from a co-culture of
metastatic C4-2 cancer cells with hydroxyapatite bone increased HMGA2 expression and paracrine cell
migration in vitro, while in vivo, more cancer cells migrated towards hydroxyapatite implant of higher bone
density. We hypothesize that HMGA2 isoforms can differentially mediate prostate cancer progression,
and that HMGA2 SNPs will be associated with higher prostate cancer incidence in Black men. Firstly,
we will examine the expression of HMGA2, both wild-type and truncated in clinical samples of patients from
different races, and the mechanism of action of wild-type vs truncated HMGA2 (Specific Aim 1). Secondly, we
will examine the correlation between HMGA2 SNPs with prostate cancer incidence (Specific Aim 2). Thirdly,
we will determine the molecular mechanisms by which HMGA2 may mediate prostate cancer interactions with
bone using in vitro and in vivo mouse models (Specific Aim 3). These studies will reveal a novel functional role
for HMGA2 in prostate health disparities.

## Key facts

- **NIH application ID:** 10134829
- **Project number:** 5U54MD007590-34
- **Recipient organization:** CLARK ATLANTA UNIVERSITY
- **Principal Investigator:** Valerie Odero-Marah
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $210,732
- **Award type:** 5
- **Project period:** 1997-06-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134829

## Citation

> US National Institutes of Health, RePORTER application 10134829, Role of High Mobility Group A2 (HMGA2) in Prostate Cancer (5U54MD007590-34). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134829. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*