Figure 8.

Hedgehog signaling components are altered in pretumorigenic Bmpr1a Bmpr1b dKO ovaries and remain elevated in tumors. A–D, QPCR analysis of components of the hedgehog signaling pathway in 3-month-old ovaries from Bmpr1a cKO, Bmpr1b^−/−, and Bmpr1a Bmpr1b dKO compared with WT ovaries; E and F, QPCR analysis of Gli1 and Gli2 expression in granulosa cells from immature WT mice that were cultured for 5 h in the absence (control) or presence of TGFβ1 (30 ng/ml); G, QPCR analysis of GLI transcription factors and GLI target gene Ptch1 in Bmpr1a Bmpr1b dKO granulosa cell tumors compared with WT granulosa cells; H, summary of hedgehog signaling pathway. Hedgehog ligands bind to PTCH receptors leading to depression of SMO and activation of GLI transcription factors, which regulate a number of target genes, one of which is Ptch1. TGFβ1 up-regulates the expression of GLI transcription factors. Data in A–D were analyzed using one-way ANOVA and Tukey's honestly significant differences test, and bars with a different letter (a–c) are significantly different at P < 0.05. Asterisks (E–G) denote statistical significance by two-tailed Student's t test: *, P < 0.05; **, P < 0.01. RQ, Relative quantity of transcript.