The Role of the Sonic Hedgehog Pathway for Prostate Cancer Progression
Abstract
The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP), are detected in over 70% of prostate tumors with Gleason scores 8-10, but in only 22% of tumors with Gleason scores 36. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. We find that Su(Fu) protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu). Furthermore, expression of sonic hedgehog protein is detected in the majority of PTCH1 positive tumors (24 out of 27). High levels of hedgehog target genes are also detected in three prostate cancer cell lines (DU145, LN-Cap and PC3). We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells. Our data indicate that activation of the hedgehog pathway, through loss of Su(Fu) or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have significant implications of prostate cancer therapeutics.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA447632
Entities
People
- Jingwu Xie
Organizations
- University of Texas Medical Branch