کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6077005 1203524 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ArticleSelective Ablation of Glucocorticoid Receptor in Mouse Keratinocytes Increases Susceptibility to Skin Tumorigenesis
ترجمه فارسی عنوان
جداسازی ماده اصلی انتخاب گیرنده گلوکوکورتیکوئید در کراتینوسیت های موش باعث افزایش حساسیت به توموری زایی پوست می شود
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
چکیده انگلیسی

We recently demonstrated that mice lacking the epidermal glucocorticoid (GC) receptor (GR) (GR epidermal knockout (GREKO) mice) have developmental defects and sensitivity to epidermal challenge in adulthood. We examined the susceptibility of GREKO mice to skin chemical carcinogenesis. GREKO mice treated with a low dose of 12-dimethylbenz(a) anthracene (DMBA) followed by phorbol 12-myristate 13-acetate (PMA) promotion exhibited earlier papilloma formation with higher incidence and multiplicity relative to control littermates (CO). Augmented proliferation and inflammation and defective differentiation of GREKO keratinocytes contributed to the phenotype, likely through increased AKT and STAT3 (signal transducer and activator of transcription 3) activities. GREKO tumors exhibited signs of early malignization, including delocalized expression of laminin A, dermal invasion of keratin 5 (K5)-positive cells, K13 expression, and focal loss of E-cadherin. Cultured GREKO keratinocytes were spindle like, with loss of E-cadherin and upregulation of smooth muscle actin (SMA) and Snail, suggesting partial epithelial-mesenchymal transition. A high DMBA dose followed by PMA promotion generated sebaceous adenomas and melanocytic foci in GREKO and CO. Importantly, the number, growth kinetics, and extent of both tumor types increased in GREKO mice, suggesting that in addition to regulating tumorigenesis from epidermal lineages, GR in keratinocytes is important for cross-talk with other skin cells. Altogether, our data reinforce the importance of GR in the pathogenesis of skin cancer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 133, Issue 12, December 2013, Pages 2771-2779
نویسندگان
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