# Molecular mechanisms specific to ETS transcription factors that drive oncogenesis

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $464,469

## Abstract

PROJECT SUMMARY/ABSTRACT
The most common alterations of the prostate cancer genome are chromosomal rearrangements that result in
aberrant expression of an ETS family transcription factor that is not normally expressed in prostate cells.
Expression of these factors, including ERG, ETV1, and ETV4, in prostate cells is oncogenic. However, there
are many other ETS factors present in normal prostate that are important for normal functions, and can even
be tumor suppressors. Thus, to devise therapies to target ETS factors in prostate cancer, it is critical to
understand specific functional mechanisms specific to oncogenic family members. Preliminary data from the
applicants' laboratory supports the central hypothesis of this proposal, which proposes that all oncogenic ETS
family members activate a similar gene expression program through specific mechanisms that are not used by
non-oncogenic ETS proteins. The following three specific aims will be used to identify specific functions of
oncogenic ETS proteins: 1) Determine the common transactivation mechanism of ETS factors that drive
prostate cancer; 2) Identify mechanisms used by signaling pathways to regulate ERG function in prostate cells;
and 3) Determine how oncogenic ETS factors function in prostate cells within the context of the ETS family.
These aims are guided by strong preliminary data including the identification of proteins that specifically
associate with oncogenic ETS proteins and not with non-oncogenic ETS proteins. In vitro and in vivo assays
will test the importance of these interactions, and mechanistic details will be determined using biochemical and
genome-wide mapping techniques. Completion of these studies will yield the first understanding of functional
mechanisms unique to oncogenic ETS proteins and provide important new molecular targets for
pharmacological strategies to prevent both the growth and progression of cancer.

## Key facts

- **NIH application ID:** 10206043
- **Project number:** 5R01CA204121-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Peter Celestine Hollenhorst
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $464,469
- **Award type:** 5
- **Project period:** 2017-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10206043

## Citation

> US National Institutes of Health, RePORTER application 10206043, Molecular mechanisms specific to ETS transcription factors that drive oncogenesis (5R01CA204121-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10206043. Licensed CC0.

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