کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914739 | 1088810 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeted Cox2 gene deletion in intestinal epithelial cells decreases tumorigenesis in female, but not male, ApcMin/+ mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mice heterozygous for mutations in the adenomatous polyposis coli gene (Apc+/â mice) develop intestinal neoplasia. Apc+/â tumor formation is thought to be dependent on cyclooxygenase 2 (COX2) expression; both pharmacologic COX2 inhibition and global Cox2 gene deletion reduce the number of intestinal tumors in Apc+/â mice. COX2 expression is reported in epithelial cells, fibroblasts, macrophages and endothelial cells of Apc+/â mouse polyps. However, the cell type(s) in which COX2 expression is required for Apc+/â tumor induction is not known. To address this question, we developed ApcMin/+ mice in which the Cox2 gene is specifically deleted either in intestinal epithelial cells or in myeloid cells. There is no significant difference in intestinal polyp number between ApcMin/+ mice with a targeted Cox2 gene deletion in myeloid cells and their control littermate ApcMin/+ mice. In contrast, ApcMin/+ mice with a targeted Cox2 deletion in intestinal epithelial cells have reduced intestinal tumorigenesis when compared to their littermate control ApcMin/+ mice. However, two gender-specific effects are notable. First, female ApcMin/+ mice developed more intestinal tumors than male ApcMin/+ mice. Second, targeted intestinal epithelial cell Cox2 deletion decreased tumorigenesis in female, but not in male, ApcMin/+ mice. Considered in the light of pharmacologic studies and studies with global Cox2 gene knockout mice, our data suggest that (i) intrinsic COX2 expression in intestinal epithelial cells plays a gender-specific role in tumor development in ApcMin/+ mice, and (ii) COX2 expression in cell type(s) other than intestinal epithelial cells also modulates intestinal tumorigenesis in ApcMin/+ mice, by a paracrine process.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 8, Issue 2, March 2014, Pages 169-177
Journal: Molecular Oncology - Volume 8, Issue 2, March 2014, Pages 169-177
نویسندگان
Durga P. Cherukuri, Tomo-o Ishikawa, Patrick Chun, Art Catapang, David Elashoff, Tristan R. Grogan, James Bugni, Harvey R. Herschman,