Fig. 10

AR induces LRIG1 to curb ERBB signaling: a model. a, b R1881-induced AR upregulation is accompanied by increased LRIG1 and dynamic downregulation of (p)ERBB members in LNCaP cells. LNCaP cells cultured in CDSS (48 h) were treated with R1881 (0.1 nM) for up to 120 h (R1881 was replenished every 24 h) and whole cell lysate (80 μg/lane) was used in WB for the molecules indicated. Protein bands were scanned by densitometry and shown in b is the quantification of average (n = 2) protein levels of AR, LRIG1, and (p)ERBB members normalized to GAPDH levels at time 0 (1.0). Note that pERBB2 (Y1221-1222) and pERBB3 (Y1289) bands were too faint to scan. pERBB3* was the (putatively) phosphorylated ERBB3 band detected by the mouse mAb against ERBB3 (Millipore 05-390; see Supplementary Table 1). As can be seen, AR induction was accompanied by increased protein levels of AR, LRIG1, EGFR, ERBB3 but decreased levels of pEGFR, ERBB2, and pERBB3. c AR knockdown reduces LRIG1 and EGFR in LNCaP cells. LNCaP cells were treated by AR-targeting siRNAs (10 nM), and whole cell lysate used in WB for the molecules indicated. The results are representative of 2 independent experiments. d–f Potential relationship between AR and (p)ERBB protein levels in the human PCa TCPA database (see Text and Methods). The correlation coefficients (R values) and P-values were determined by linear regression analyses. g A model depicting that LRIG1 is feedback induced by three major signaling pathways in PCa, i.e., AR, c-MYC, and ERBBs, to neutralize/antagonize their oncogenic activities. The model also depicts cross-regulatory relationship between AR and ERBBs. *Source data for Fig. 10 (representative gel images) are provided as a Source Data file.