Fig. 7. Persistent and increased LRIG1 expression in CRPC.
(A) Heterogeneous LRIG1 mRNA expression in CRPC. Shown are the relative LRIG1 mRNA levels in CRPC compared to corresponding hormone-naïve PCa in 3 Oncomine datasets. LRIG1 was upregulated in the Tomlins dataset (FC = 2.359; p = 0.009) and showed reduced trend in the Best dataset (FC= −1.635; p = 0.095) whereas LRIG1 did not change in Holzbeirlein dataset (FC = 1.029; p = 0.483). (B) Discordant LRIG1 and AR expression and persistently high LRIG1 expression in patient CRPC. Shown are matched IHC images of AR and LRIG1 in the whole-mount slides of 4 patient CRPC specimens (adapted with permission from [100]). Note that most CRPC cells lost AR expression but retained high levels of LRIG1. (C) Persistent LRIG1 expression in CRPC xenograft models. Whole cell lysates (60 μg/lane) prepared from 4 pairs of androgen-dependent (AD) and androgen-independent (AI; castration-resistant) xenograft tumors (lanes 1-8) and from 1 pair of in vitro castrated (i.e., CDSS for 48 h) LNCaP cells (lanes 9-10) were used in WB analysis of the molecules indicated. (D) Alterations of LRIG1 in an in vitro castration model. As detailed in [108], LNCaP cells were subjected to 3 regimens of long-term castration in culture, i.e., CDSS (charcoal dextran stripped serum), ENZA (enzalutamide; 10 μM), or CDSS plus bica (bicalutamide; 20 μM) for the time intervals indicated (w, week; m, month). Whole cell lysates (60 μg/lane) were used in WB analysis of the molecules indicated. *, cleaved ~110-kD and 100-kD LRIG1 ECD fragments. The arrow indicates the 60-kD ECD fragment.