Activation of hedgehog signaling is not a frequent event in ovarian cancers

Abstract

The hedgehog (Hh) signaling pathway regulates many processes of development and tissue homeostasis. Activation of hedgehog signaling has been reported in about 30% of human cancer including ovarian cancer. Inhibition of hedgehog signaling has been pursued as an effective strategy for cancer treatment including an ongoing phase II clinical trial in ovarian cancer. However, the rate of hedgehog signaling activation in ovarian cancer was reported differently by different groups. To predict the successful for future clinical trials of hedgehog signaling inhibitors in ovarian cancer, we assessed hedgehog pathway activation in 34 ovarian epithelial tumor specimens through analyses of target gene expression by in-situ hybridization, immunohistochemistry, RT-PCR and real-time PCR. In contrast to previous reports, we only detected a small proportion of ovarian cancers with hedgehog target gene expression, suggesting that identification of the tumors with activated hedgehog signaling activation will facilitate chemotherapy with hedgehog signaling inhibitors.

Figure 1

Expression of PTCH1, GLI1 and HIP1 in ovarian cancer. PTCH1, GLI1 and HIP transcript (blue as positive) was detected by in situ hybridization in a well-differentiated serous papillary adenocarcinoma (the left panel), and the right panel pictures are their controls with respective sense probes (Bars indicate 50 μm).

Figure 2

PCR detection of hedgehog signaling in ovarian cancer specimens. A. Real-time PCR analysis of GLI1 expression in ovarian cancer was performed as described in Materials and Methods. Gli1 transcript was shown here. B. PCR detection of SHH, PTCH1, GLI1, SMO, HIP1 and Su(Fu) transcripts in ovarian cancers. GAPDH is the endogenous control. Numbers listed indicate specimen number.

Figure 3

Expression of PTCH1, SHH and SMO protein in ovarian cancer. PTCH1, SHH and SMO protein (yellow as positive) was detected by immunohistochemistry in a poorly-differentiated serous papillary adenocarcinoma (left panel), and the right panel pictures are controls without primary antibody (Bars indicate 50 μm).

Figure 4

Expression of SHH, SMO and Su(Fu) in ovarian cancer. SHH, SMO and Su(Fu) transcript (blue as positive) was detected by in situ hybridization. The positive stain of SHH, SMO was shown in a well-differentiated serous papillary adenocarcinoma and the positive stain of Su(Fu) was shown in a poorly-differentiated serous papillary adenocarcinoma (left panel), and the right panel pictures are controls of in situ hybridization with respective sense probe (the bar indicates 50 μm).