Figure 4. TSC2 negatively regulates AdPLA2 expression in vivo.

Female CB17-scid mice were subcutaneously inoculated with ELT3-V3 cells (TSC2-, vector) or ELT3-T3 (TSC2+, TSC2 addback) cells (n = 8 mice/group). (A) Immunoblotting analysis of AdPLA2 and phospho-S6 (S235/236) in xenograft tumors of ELT3 cells. A densitometry analysis of AdPLA2 was performed. (B) Urinary levels of PGE₂ were quantified using ELISA and normalized to creatinine levels in mice bearing xenograft tumors. Results are representative of five to nine mice per group. C) Immunohistochemical staining of AdPLA2 in xenograft tumors of Tsc2-deficient rat-derived ELT3 cells and lungs of mice treated with placebo or estrogen. Arrowheads point to lung metastatic lesions in estradiol-treated mice bearing xenograft tumors of ELT3 cells. (D) Tsc2^+/− mice were treated with either vehicle or Celecoxib (Pfizer) (0.1% in mouse chow) for one month, and then sacrificed for analysis at the end of treatment (n = 3 mice/group). Immunohistochemical staining of AdPLA2 in renal cystadenomas from Tsc2 ^+/−mice was performed. *P<0.05, **P<0.01, Student’s t-test.