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Detection of Canonical Hedgehog Signaling in Breast Cancer by 131-Iodine-Labeled Derivatives of the Sonic Hedgehog Protein
- Source :
- Journal of Biomedicine and Biotechnology, Journal of Biomedicine and Biotechnology, Vol 2012 (2012)
- Publication Year :
- 2012
- Publisher :
- Hindawi Publishing Corporation, 2012.
-
Abstract
- Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is overexpressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of131I-SHH was increased in cell lines with high HH pathway activation. Our findings also show that PTCH-1 receptor expression is decreased upon treatment with HH signaling inhibitors, and receptor binding of131I-SHH is significantly decreased following treatment with cyclopamine.In vivoimaging and biodistribution studies revealed significant accumulation of131I-SHH within tumor tissue as compared to normal organs. Tumor-to-muscle ratios were approximately 8 : 1 at 5 hours, while tumor to blood and tumor to bone were 2 : 1 and 5 : 1, respectively. Significant uptake was also observed in liver and gastrointestinal tissue. These studies show that131I-SHH is capable ofin vivodetection of breast tumors with high HH signaling. We further demonstrate that the hedgehog receptor PTCH-1 is downregulated upon treatment with hedgehog inhibitors. Our data suggests that radiolabeled SHH derivatives may provide a method to determine response to SHH-targeted therapies.
- Subjects :
- Health, Toxicology and Mutagenesis
Receptor expression
lcsh:Medicine
Iodine Radioisotopes
chemistry.chemical_compound
Tissue Distribution
Receptor
Oncogene Proteins
Veratrum Alkaloids
General Medicine
Hedgehog signaling pathway
Patched-1 Receptor
Isotope Labeling
embryonic structures
Molecular Medicine
Biological Assay
Female
Signal transduction
Biotechnology
Research Article
Protein Binding
Signal Transduction
Patched
Patched Receptors
medicine.medical_specialty
animal structures
Article Subject
Cyclopamine
lcsh:Biotechnology
Blotting, Western
Breast Neoplasms
Receptors, Cell Surface
Biology
Zinc Finger Protein GLI1
Internal medicine
lcsh:TP248.13-248.65
Cell Line, Tumor
Genetics
medicine
Sonic Hedgehog Protein
Animals
Humans
Gamma Cameras
Hedgehog Proteins
Radiometry
Radionuclide Imaging
Molecular Biology
Hedgehog
Cell Proliferation
lcsh:R
Xenograft Model Antitumor Assays
Rats, Inbred F344
Rats
Endocrinology
chemistry
Cancer research
Trans-Activators
Subjects
Details
- Language :
- English
- ISSN :
- 11107251 and 11107243
- Volume :
- 2012
- Database :
- OpenAIRE
- Journal :
- Journal of Biomedicine and Biotechnology
- Accession number :
- edsair.doi.dedup.....c7c68f3ee88d6fdd73d020b90f612a8d