Figure 7. LYPD3 as a Candidate Drug Target for the Treatment of Aggressive Luminal Cancer.

(A) TAMR cells were transfected with siCtrl or three unique siRNA sequences targeting LYPD3 and monitored for 9 days. Individual points on the curve represent the mean relative fluorescent intensity of triplicate wells per condition on that day. Error bars calculated as SEM. The experiment was repeated three times with similar results, and representative data are shown.

(B) Tamoxifen-treated J:nu mice bearing TamR xenograft tumors were randomized to treatment with 45 mg/kg IgG, 15 mg/kg anti-AGR2 (top), or 45 mg/kg anti-LYPD3 (bottom) antibodies intraperitoneally (i.p.) twice weekly, with groups further subdivided to receive subcutaneous (s.c.) injection of corn oil or 25 mg/kg fulvestrant. To facilitate interpretation, data for anti-AGR2 and anti-LYPD3 are presented in separate graphs, with controls (IgG and fulvestrant administered alone) included in both graphs. Data presented indicate the average tumor volume for each group (mean ± SEM) at each time point of tumor measurement. Two-way ANOVA analysis followed by Bonferroni multiple-comparison test detected significant differences between the IgG control and all treatment groups between days 14 and 28 (*p < 0.05).

(C) TAMR tumors from mice treated with corn oil (vehicle) or fulvestrant were assessed for mRNA expression of KRT13 and LYPD3; n = 9 xenograft tumors per group. Data plotted are mean fold change ± SEM.

(D and E) LYPD3 mRNA (D) and protein expression (E) was assessed in LTED tumors and compared with representative samples of MCF7-WS8 and TAMR tumors. Each bar indicates an independent biological replicate and plotted as mean fold change ± SD (three technical replicates). Asterisk indicates samples with mRNA expression significantly different (p < 0.05) than a representative MCF7-WS8 control tumor sample.

See also Figures S6 and S7.