The ovarian steroid hormones, estradiol and progesterone, and their nuclear receptors (estrogen receptor [ER] and progesterone receptor [PR]), are involved in breast cancer development. As ER-positive/PR-positive tumors progress, they are likely to become steroid hormone-resistant/independent, yet often retain expression of their steroid receptors. Notably, up to 40% of women with steroid receptor-positive tumors exhibit de novo resistance or eventually fail on estrogen- or ERα-blocking therapies (acquired resistance). Indeed, most of the research on this topic has centered on mechanisms of ER 'escape' from endocrine therapy and the design of better ER-blocking strategies; signaling pathways that mediate endocrine (i.e., anti-estrogen) resistance are also excellent therapeutic targets. However, serious consideration of PR isoforms as important drivers of early breast cancer progression and ER modulators is timely and significant. Indeed, progress has been hindered by ER-centric experimental approaches. This article will focus on defining a role for PR in breast cancer with hopes of providing a refreshing PR-focused perspective.
Bibliographical noteFunding Information:
This work was supported by a grant from the National Institutes of Health (NIH/National Cancer Institute): R01 CA123763 (formerly R01 DK53825; NIH/National Institute of Diabetes and Digestive and Kidney Diseases). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Copyright 2011 Elsevier B.V., All rights reserved.
- breast cancer
- estrogen receptor
- hormone replacement therapy
- mammary gland biology
- progesterone receptor
- protein kinases
- stem cells