کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4132993 1271405 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aldoketoreductase family 1B10 (AKR1B10) as a biomarker to distinguish hepatocellular carcinoma from benign liver lesions
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی آسیب‌شناسی و فناوری پزشکی
پیش نمایش صفحه اول مقاله
Aldoketoreductase family 1B10 (AKR1B10) as a biomarker to distinguish hepatocellular carcinoma from benign liver lesions
چکیده انگلیسی

SummaryHepatocellular carcinoma (HCC) is one of the most common highly aggressive malignant tumors worldwide. Aldoketoreductase 1B10 (AKR1B10) was first isolated from HCC and further identified to be over-expressed in many cancers from various organs. AKR1B10 contributes to detoxification of xenobiotics by lipid peroxidation and metabolizes physiological substrates such as farnesal, retinal, and carbonyls. Metabolizing these lipid substrates plays a crucial role in promoting carcinogenesis. In the present study, immunohistochemical analysis was performed to determine the prevalence/pattern of AKR1B10 expression in HCC and its usefulness to differentiate benign liver lesions from HCC. Oncogenic function of AKR1B10 was examined in hepatocellular carcinoma cells in vitro using Western blotting and shRNA knockdown approaches, with emphasis on cell apoptosis and response to chemotherapy. Immunohistochemistry analysis revealed AKR1B10 was overexpressed in 97% (86/89) of hepatocellular carcinomas, with minimal to no expression in adjacent hepatic tissue, while hepatic adenomas and focal nodular hyperplasia did not exhibit expression of AKR1B10. shRNA-mediated silencing of AKR1B10 expression in hepatocellular carcinoma cells resulted in (1) increased cell apoptosis, (2) decreased colony formation and size, and (3) enhanced cytoreductive response following exposure to doxorubicin chemotherapy. Our findings provide first time evidence that AKR1B10 is a unique biomarker involved in hepatocellular carcinogenesis via modulation of proliferation, cell apoptosis and chemoresistance and is a potential promising biomarker to differentiate HCCs from benign hepatic lesions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Human Pathology - Volume 45, Issue 4, April 2014, Pages 834–843
نویسندگان
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