Influence of stromal–epithelial interactions on androgen action

Abstract

Androgen receptor (AR) signaling is vital to the development and function of the prostate and is a key pathway in prostate cancer. AR is differentially expressed in the stroma and epithelium, with both paracrine and autocrine control throughout the prostate. Stromalepithelial interactions within the prostate are commonly dependent on AR signaling and expression. Alterations in these pathways can promote tumorigenesis. AR is also expressed in normal and malignant mammary tissues. Emerging data indicate a role for AR in certain subtypes of breast cancer that has the potential to be exploited therapeutically. The aim of this review is to highlight the importance of these interactions in normal development and tumorigenesis, with a focus on the prostate and breast.

The role of the prostate in male fertility, health and disease

“…The stromal compartment provides many supportive signals to retain or restore gland homeostasis in healthy conditions or during regeneration processes. Several lines of evidence also indicate that activated stroma might have a pivotal role in prostate inflammatory processes 5 .…”

“…The prostate epithelial compartment has the main glandular function as it secretes the prostatic fluid that constitutes approximately one-fifth to one-third of the volume of the entire ejaculate [1][2][3][4][5] . The prostatic fluid, as with the other secretions of the male accessory glands, is an essential contributor to male fertility.…”

“…Human seminal plasma is a very complex bodily fluid, the composition of which is strictly regulated by the hypothalamic-pituitary-adrenal (HPA) axis via the gonadotrophic or hypothalamic-pituitary-gonadal (HPG) axis. Seminal plasma composition is also affected by the metabolic and psychological state of the organism 1-3 , and coordinates the action of all of the different 'players' involved in fertility within the human male reproductive system 4,5 .…”

Androgen receptor in male breast cancer

“…AR plays an essential role in the developmentandmaintenanceofnormalglandularorganizationandintegrity.AberrantARresponsescanlead tothedisruptionresultingintumorigenesis [28].AR positivityisdetectedinapproximately70-80%ofall breast cancer cases and it is associated with favourable outcomes, especially in patients with ER-positivetumors [2,19,29,30,31,32].…”

Androgen signalling and steroid receptor crosstalk in endocrine cancers

“…Androgens in breast and other female tissues Nieto et al (2014) summarise the growing evidence on the significance of AR signalling in breast development and homoeostasis in female mice, while McNamara et al (2014) and Tarulli et al (2014) focus on the emerging role of the AR in breast cancer. It has been known for decades that AR is expressed in a large proportion of breast cancers and that clinical and laboratory evidence indicated that AR signalling regulates the activity of breast cancer cells.…”