Abstract
Hepatocellular carcinoma (HCC) is the fourth most common malignancy and one of the leading causes of death world wide. Signaling pathways important for tumor initiation and progression in HCC are poorly understood. Hedgehog signaling (Hh) has been implicated in multiple events during development and has also been proposed to play important roles in several tumor types. However, it remains unclear whether this pathway is activated in HCC. Here, we report the detection of transcripts for hedgehog pathway signaling molecules in both HCC cell lines and tumor samples. Quantitative real-time RT-PCR also revealed the decreased expression of Hip1 and increased expression of Gli1 and smo in HCC samples compared with nontumor liver tissues. Blocking the hedgehog pathway with cyclopamine inhibited proliferation, induced apoptosis and repressed c-Myc and cyclin D expression in a subset of HCC cell lines. The study therefore, for the first time, provides evidence that hedgehog signaling may be activated in some HCC tumors. The results also indicate that the hedgehog pathway may be a new candidate for therapeutic targeting in HCC.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism*
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Cell Proliferation / drug effects
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Cyclin D
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Cyclins / antagonists & inhibitors
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Hedgehog Proteins
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Humans
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism*
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Oncogene Proteins / antagonists & inhibitors
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Patched Receptors
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Proto-Oncogene Proteins c-myc / antagonists & inhibitors
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription, Genetic
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Veratrum Alkaloids / pharmacology
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Zinc Finger Protein GLI1
Substances
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Cyclin D
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Cyclins
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DNA-Binding Proteins
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HIP1 protein, human
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Hedgehog Proteins
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MYC protein, human
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Oncogene Proteins
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Patched Receptors
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Proto-Oncogene Proteins c-myc
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Receptors, Cell Surface
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Trans-Activators
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Veratrum Alkaloids
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Zinc Finger Protein GLI1
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cyclopamine