Peroxisome Proliferator-Activated Receptor as a Therapeutic Target in Human Breast Cancer
Julie M. Hall* and Matthew L. Robinson
Department of Pharmaceutical Sciences, Campbell University, College of Pharmacy & Health Sciences, Buies Creek, NC, USA
- *Corresponding Author:
- Julie M. Hall
Campbell University, College of Pharmacy & Health Sciences
Box 1090, Buies Creek, NC 27506, USA
E-mail: [email protected]
Received date: May 04, 2015; Accepted date: May 22, 2015; Published date: May 29, 2015
Citation: Hall JM, Robinson ML (2015) Peroxisome Proliferator-Activated Receptor γ as a Therapeutic Target in Human Breast Cancer. J Steroids Hormon Sci 6:155. doi:10.4172/2157-7536.1000155
Copyright: © 2015 Hall JM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Peroxisome proliferator-activated receptor γ (PPARγ) is aberrantly expressed in most breast tumors, suggesting the potential of agents that target this receptor in treatment and chemoprevention of breast cancer. However, whether PPARγ leads to the promotion or reduction of tumor formation has remained controversial and is further complicated by the ability of its available thiazolidinedione (TZD) ligands to activate another PPAR subtype, PPARδ.
Method: To examine the role of each receptor in breast cancer biology, we performed a systematic evaluation of PPARγ and PPARδ agonists on the growth of human estrogen receptor (ER)-positive and -negative breast cancer cells.
Results: In this manner we found that TZD-activated PPARγ was highly effective in suppressing the proliferation of estrogen-dependent cancer cells. Activated PPARδ, however, displayed growth-enhancing effects independent of estradiol and regardless of the ER status of the cells. Strikingly, in ER-negative cancer cells expressing a favorable PPARδ/γ ratio, TZDs promoted growth in a PPAR γ-independent manner by direct activation of PPARδ. A screen for ligands with increased receptor selectivity compared to TZDs revealed that GW7845 functioned as a full agonist of PPARγ, yet this agent lacked the ability to activate PPARδ and elicit its associated mitogenic effects.
Conclusion: These studies indicate that selective PPAR γ modulators (SPPARγMs) that lack agonist activity on PPARδ may be clinically useful in future cancer treatment and chemoprevention.