Caveolin-1 Interacts with Androgen Receptor

Abstract

Androgen receptor (AR) belongs to the steroid hormone nuclear receptor superfamily. It functions as an androgen-dependent transcriptional factor that regulates genes for cell proliferation and differentiation. Caveolin is a principal component of caveolae membranes serving as a scaffold protein of many signal transduction pathways. Recent results correlate caveolin-1 expression with androgen sensitivity in murine prostate cancer. Furthermore, immunohistochemical staining of patient specimens suggests that caveolin expression may be an independent predictor of progression of prostate cancer. In this study, we investigate the potential interactions between AR signaling and caveolin-1 and demonstrate that overexpression of caveolin-1 potentiates ligand-dependent AR activation. Conversely, down-regulation of caveolin-1 expression by a caveolin-1 antisense expression construct can downregulate ligand-dependent AR activation. Association between these two molecules is also demonstrated by co-localization of AR with caveolin-rich, low-density membrane fractions isolated by an equilibrium sucrose gradient centrifugation method. Co-immunoprecipitation and glutathione S-transferase fusion protein pulldown experiments demonstrate that interaction between AR and caveolin-1 is an androgen-dependent process, offering further evidence for a physiological role of this interaction. Using a mammalian two-hybrid assay system, we determine that the NH 2 terminus region of caveolin-1 is responsible for the interaction with both the NH 2 -terminal domain and the ligand-binding domain of AR.

Androgen receptor signalling in prostate: Effects of stromal factors on normal and cancer stem cells

“…Expression has been detected in both epithelium and stroma and has been correlated with CaP progression (Lu et al, 2001), as is also the case in primary and metastatic breast cancer (Yang et al, 1998). Over expression of caveolin 1…”

“…Co-localization of AR with caveolin-rich membrane regions is androgen dependent and an interaction with the AR ligand-binding domain has been shown (Lu et al, 2001). ER can also interact directly with caveolin 1, and since both AR and ER are expressed by the stroma, this underlines the importance of caveolin 1 to prostate stroma (Freeman et al, 2005).…”

“…Caveolin is a component of caveolae membranes which function as a scaffold protein and can associate with EGFR and insulin receptor (Lu et al, 2001). Expression has been detected in both epithelium and stroma and has been correlated with CaP progression (Lu et al, 2001), as is also the case in primary and metastatic breast cancer (Yang et al, 1998).…”

Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation

“…Interaction with and modulation by caveolin-1 have been shown in many signal transduction pathways, including those regulated by steroids receptors or tyrosine kinase receptors. Hence, caveolin-1 has been shown to associate and regulate activation of androgen receptor (AR) (Lu et al, 2001), estrogen receptor (ER) (Schlegel et al, 1999(Schlegel et al, , 2001, epidermal growth factor receptor (Couet et al, 1997) and insulin receptor (Yamamoto et al, 1998). Particularly, transcriptional activities of ER and AR have been shown to be potentiated by caveolin-1 (Lu et al, 2001;Schlegel et al, 2001).…”

“…Hence, caveolin-1 has been shown to associate and regulate activation of androgen receptor (AR) (Lu et al, 2001), estrogen receptor (ER) (Schlegel et al, 1999(Schlegel et al, , 2001, epidermal growth factor receptor (Couet et al, 1997) and insulin receptor (Yamamoto et al, 1998). Particularly, transcriptional activities of ER and AR have been shown to be potentiated by caveolin-1 (Lu et al, 2001;Schlegel et al, 2001). Even though caveolin-1 interaction with many of the signal transduction components is thought to have important consequences for cellular transformation; the role of caveolin-1 in cancer still remains controversial.…”