Figure 5. Changes in protein expression and activation of signaling proteins associated with HSP90 inhibition.

(A) Differences in expression of phosphorylated Y¹⁰⁶⁸ and Y¹¹⁷³ EGFR and total EGFR normalized to actin, and Y¹⁰⁶⁸ and Y¹¹⁷³ EGFR normalized to total EGFR, following treatment with the indicated doses of STA-2842. *, P<0.05; **, P<0.01. (B) Insignificant differences in expression of phosphorylated T²⁰²/Y²⁰⁴ ERK1/2 or total ERK1/2, normalized to tubulin, and phosphorylated T²⁰²/Y²⁰⁴ ERK1/2 normalized to total ERK1/2, following treatment with the indicated doses of STA-2842; differences are not significant (C) Positive correlations between the ratio of phosphorylated T²⁰²/Y²⁰⁴ ERK1/2 normalized to total ERK1/2 expression in the drug treatment groups and (left) cyst volume/region of interest (ROI) (P = 0.174) and (right) liver weight/body weight (lw/bw) ratio (P = 0.040). Dots represent individual mice; lines represent linear regression functions. n = 6–8 mice. All data graphed as mean ± standard error of the mean (SEM). (D) Expression of phosphorylated T²⁰²/Y²⁰⁴ ERK1/2 in cystic epithelia (left) or total liver (right) quantified from immunohistochemical staining of liver sections from Pkd1 ^–/– mice treated with vehicle or 100 mg/kg STA-2842 (see Fig S4). **, P<0.01. (E) Differences in expression of phosphorylated phS²³⁵/S²³⁶ S6 or total S6, normalized to tubulin, and phosphorylated phS²³⁵/S²³⁶ S6 normalized to total S6, following treatment with the indicated doses of STA-2842; *, P<0.05. P-values for comparisons between Pkd1 ^–/– vehicle- versus 100 mg/kg-treated groups bordering on significant (P = 0.060). (F) Differences in expression of phosphorylated phS⁴⁷³ AKT or total AKT, normalized to tubulin, and phosphorylated phS⁴⁷³ AKT normalized to total AKT, following treatment with the indicated doses of STA-2842; *, P<0.05.