Triple negative breast cancer (TNBC) is characterized by lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). Available chemotherapy for TNBC results in limited efficacy and significant toxicity. The majority of patients with metastatic disease do not survive beyond 3 years. Currently, no targeted therapies are available for TNBC, in part because it is a highly heterogeneous disease and because the molecular drivers for TNBC are not known. TNBC more frequently affects younger patients (< 50 years) and is twice as prevalent in African American women as compared to Caucasians. There is a need to understand the biology of TNBC at the basic genetic and epigenetic levels to be able to develop targeted therapies for individual patients. We have identified a cohort of long non-coding RNAs (lncRNAs) that may be specific to TNBC in African American women. The proposed research is focused on understanding the function of these lncRNAs in TNBCs. We hypothesize that disparities in TNBC in the African American population may be explained, in part, by expression of non-coding RNAs and epigenetic alterations that are specific to this population. We propose that lncRNAs may play an important role in the initiation and progression of TNBC in this population through regulation of gene expression. This proposal, consisting of two Specific Aims, will powerfully harness the complementary expertise of a team of investigators with considerable experience in signal transduction, cell cycle control, gene regulation, and clinical aspects of breast cancer.
In Aim 1, we will test the hypothesis that down-regulation of selected driver lncRNAs will significantly affect TNBC cell proliferation, cell cycle progression, survival, migration, and invasion in TNBC using in vitro models of this disease.
In Aim 2, we propose to characterize the most promising lncRNAs using an animal model, in an effort to understand how they initiate and maintain the TNBC phenotype and the associated gene expression signature.

Public Health Relevance

TNBC is more frequent in younger patients (< 50 years) and is twice as prevalent in African American women as compared to Caucasians. We propose that lncRNAs play an important role in the initiation and progression of TNBC in this population through regulation of gene expression and will test the role of these regulatory RNAs in vitro and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA220518-02
Application #
9571236
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Schwartz, Elena Ivan
Project Start
2017-09-25
Project End
2019-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
New York University
Department
Pathology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016