کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3944520 1600077 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Frequent inactivation of RUNX3 in endometrial carcinoma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی زنان، زایمان و بهداشت زنان
پیش نمایش صفحه اول مقاله
Frequent inactivation of RUNX3 in endometrial carcinoma
چکیده انگلیسی

ObjectiveOur objective was to determine whether RUNX3 tumor suppressor is inactivated in endometrial carcinoma.MethodsWe have investigated 24 endometrial carcinomas, 3 endometrial carcinoma cell lines, and 9 normal endometria for genetic and epigenetic alterations of RUNX3. Reverse-transcription PCR (RT-PCR), methylation-specific PCR (MS-PCR) analysis, and loss of heterozygosity (LOH) analysis were performed. We also tested RUNX3 protein expression by immunohistochemistry.ResultsUsing RT-PCR technique, we observed a significant loss of RUNX3 mRNA expression in nine of 24 endometrial carcinomas (38%) and in all 3-cell lines (100%). In contrast, all nine of the normal endometria showed an abundant expression of RUNX3 mRNA. Methylation-specific PCR (MS-PCR) analysis of the CpG islands of RUNX3 showed the promoter region to be hypermethylated in 18 of 21 analyzed carcinomas (86%), whereas only two of nine normal endometria (22%) were methylated (p < 0.01). By using two polymorphic microsatellite markers, D1S199 and D1S1676, we detected 1p36 LOH in 7 of 21 carcinomas (33%). We observed a significant relationship between the loss of RUNX3 mRNA expression and this regional LOH (p < 0.01). Immunohistochemical staining showed that RUNX3 protein expression was lost in 12 of 21 endometrial carcinomas (57%). We observed a significantly more frequent loss of RUNX3 protein expression in the histologically higher-grade tumors (Grade 3) than in Grade 1 or 2 tumors (p < 0.01).ConclusionThese findings indicate that RUNX3 inactivation may play an important role in carcinogenesis of the endometrium, especially in high-grade endometrial carcinoma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gynecologic Oncology - Volume 110, Issue 3, September 2008, Pages 439–444
نویسندگان
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