Oncotarget

Research Papers:

Estrogen receptor-beta is a potential target for triple negative breast cancer treatment

David Austin, Nalo Hamilton, Yahya Elshimali, Richard Pietras, Yanyuan Wu and Jaydutt Vadgama _

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Oncotarget. 2018; 9:33912-33930. https://doi.org/10.18632/oncotarget.26089

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Abstract

David Austin1, Nalo Hamilton2, Yahya Elshimali1, Richard Pietras3,4, Yanyuan Wu1 and Jaydutt Vadgama1,3,4

1Department of Medicine, Division of Cancer Research and Training, Charles Drew University School of Medicine and Science, Los Angeles, CA 90059, USA

2UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA 90095, USA

3UCLA Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90095, USA

4UCLA David Geffen School of Medicine, Department of Medicine, Division of Hematology-Oncology, University of California at Los Angeles, Los Angeles, CA 90095, USA

Correspondence to:

Jaydutt Vadgama, email: jayvadgama@cdrewu.edu

Keywords: estrogen receptor-beta; triple negative breast cancer; insulin-like growth factor 2; DPN; estrogen receptor-beta signaling

Received: December 06, 2017    Accepted: July 12, 2018    Published: September 21, 2018

ABSTRACT

Triple Negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2. TNBC accounts for 15-20% of all breast cancer cases but accounts for over 50% of mortality. We propose that Estrogen receptor-beta (ERβ) and IGF2 play a significant role in the pathogenesis of TNBCs, and could be important targets for future therapy.

Tissue microarrays (TMAs) from over 250 TNBC patients’ were analyzed for ERβ and IGF2 expression by immunohistochemistry. Expression was correlated with clinical outcomes. In addition, TNBC cell lines Caucasians (CA): MB-231/BT549 and African Americans (AAs): MB-468/HCC70/HCC1806 were used to investigate the effect of hormonal and growth factor regulation on cell proliferation.

TMAs from AAs had higher expression of ERβ and IGF2 expression when compared to CA. ERβ and IGF2 were found to be upregulated in our TNBC cell lines when compared to other cell types. TNBC cells treated with ERβ agonist displayed significant increase in cell proliferation and migration when compared to controls. AA tissue samples from TNBC patients had higher expression of ERβ. African-American breast cancer TNBC tissue samples from TNBC patients have higher expression of ERβ. In addition, TNBC cell lines were also found to express high levels of ERβ. IGF2 increased transcription of ERβ in TNBC cells. Understanding the mechanisms of IGF2/ERβ axis in TNBC tumors could provide an opportunity to target this aggressive subtype of breast cancer.


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