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Role of GAL3ST1 in Renal Cell CarcinomaGreer, Samantha Nicole 20 November 2012 (has links)
Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy characterized by
inactivation of the von Hippel-Lindau tumour suppressor gene, the protein product of
which mediates degradation of the transcription factor hypoxia-inducible factor (HIF). GAL3ST1 is a sulfotransferase which catalyzes the production of sulfatide, a plasma membrane sulfolipid previously implicated in metastasis. We observed GAL3ST1
overexpression in primary ccRCC tumours relative to matched-normal tissue and
subsequently asked if GAL3ST1 was a HIF-responsive gene that facilitates ccRCC
metastasis. GAL3ST1 expression was suppressed in ccRCC cells by stable reconstitution of wild-type VHL and also siRNA-mediated knockdown of HIF1alpha and HIF2alpha. Dual luciferase assays and chromatin immunoprecipitation revealed a hypoxia-response element in the GAL3ST1 5’-UTR that appeared to be crucial for HIF-mediated
upregulation. Finally, stable knockdown of GAL3ST1 significantly impeded ccRCC cell
invasion through an in vitro basement membrane mimic. These results suggest GAL3ST1 is a HIF-responsive gene that promotes tumour cell invasion.
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2 |
Role of GAL3ST1 in Renal Cell CarcinomaGreer, Samantha Nicole 20 November 2012 (has links)
Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy characterized by
inactivation of the von Hippel-Lindau tumour suppressor gene, the protein product of
which mediates degradation of the transcription factor hypoxia-inducible factor (HIF). GAL3ST1 is a sulfotransferase which catalyzes the production of sulfatide, a plasma membrane sulfolipid previously implicated in metastasis. We observed GAL3ST1
overexpression in primary ccRCC tumours relative to matched-normal tissue and
subsequently asked if GAL3ST1 was a HIF-responsive gene that facilitates ccRCC
metastasis. GAL3ST1 expression was suppressed in ccRCC cells by stable reconstitution of wild-type VHL and also siRNA-mediated knockdown of HIF1alpha and HIF2alpha. Dual luciferase assays and chromatin immunoprecipitation revealed a hypoxia-response element in the GAL3ST1 5’-UTR that appeared to be crucial for HIF-mediated
upregulation. Finally, stable knockdown of GAL3ST1 significantly impeded ccRCC cell
invasion through an in vitro basement membrane mimic. These results suggest GAL3ST1 is a HIF-responsive gene that promotes tumour cell invasion.
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