کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832792 1163846 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterisation of a new C1 inhibitor mutant in a patient with hepatocellular carcinoma
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Characterisation of a new C1 inhibitor mutant in a patient with hepatocellular carcinoma
چکیده انگلیسی

A patient developed the first case of hepatocarcinoma associated with hereditary angioedema within the context of a 13-year long prophylactic danazol exposure. We sought to identify the molecular defect and to test the relative contribution to the development of hepatocarcinoma of intracellular accumulation of abnormal C1 inhibitor (C1-INH) protein. The de novo mutation c.878_881delTCTA was identified, leading to a premature stop codon. Monocyte C1-INH secretions of the patient and of her affected daughter were, respectively, 26 and 18% compared to controls. Mutant transcripts compatible with the 4 bp deletion were detectable as a faint RT-PCR product both in interferon-stimulated monocytes and in liver tissue, whereas total C1-INH mRNA was found nearly half the amount recovered from normal subjects. In order to study the consequences at the protein level of the low expression of the mutant allele, we analysed the intracellular fate of mutant products. COS-7 cells were transiently transfected with a C1-INH expression minigene encoding the mutant protein. In pulse-chase experiments, a faint 75,000-Mr band was detected only within 10 min.Both the c.878_881delTCTA mutant transcript and the intracellular abnormal C1-INH protein are unstable. Our data therefore rule out the hypothesis of an accumulation of the mutant protein at levels relevant for the pathology and strengthen the link between the development of hepatocarcinoma and danazol exposure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 43, Issue 14, July 2006, Pages 2161–2168
نویسندگان
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