کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6074884 | 1203489 | 2016 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Loss of CRABP-II Characterizes Human Skin Poorly Differentiated Squamous Cell Carcinomas and Favors DMBA/TPA-Induced Carcinogenesis
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کلمات کلیدی
EGF12-O-tetradecanoyl-phorbol-13-acetatepEGFRFABP5RXRRARCRABP-IIPDGFpAktPPARDMBAmRNAtPAERK7,12-Dimethylbenz[a]anthracene - 7،12-Dimethylbenz [a] آنتراسنatRA - ATRAmessenger RNA - RNA messengerv-akt murine thymoma viral oncogene homolog 1 - v-ACT ویروس آنفولانزای ویروسی ویروسی توموما 1Akt - آکتRetinoic acid - رتینوئیک اسیدepidermal growth factor - عامل رشد اپیدرمیplatelet-derived growth factor - فاکتور رشد حاصل از پلاکتphosphorylated Akt - فسفروئید آکتGrade - مقطع تحصیلیknockout - ناکاوتwild type - نوع وحشیPERK - پرکphosphorylated extracellular signal-regulated kinase - کیناز تنظیم شده سیگنال تنظیم شده خارج سلولی فسفورید شدهextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیRetinoic acid receptor - گیرنده اسید رتینوئیکperoxisome proliferator-activated receptor - گیرنده فعال فعال پروکسیوم
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Loss of CRABP-II Characterizes Human Skin Poorly Differentiated Squamous Cell Carcinomas and Favors DMBA/TPA-Induced Carcinogenesis Loss of CRABP-II Characterizes Human Skin Poorly Differentiated Squamous Cell Carcinomas and Favors DMBA/TPA-Induced Carcinogenesis](/preview/png/6074884.png)
چکیده انگلیسی
Retinol and its derivatives play an important role in epidermal growth and differentiation and represent chemopreventive agents in nonmelanoma skin cancer. Retinoic acid binding protein II (CRABP-II) is a cytoplasmic receptor that critically regulates all-trans-retinoic acid (ATRA) trafficking. We documented the marked reduced expression of CRABP-II and its promoter methylation in human poorly differentiated squamous cell carcinomas. To investigate the role of CRABP-II in skin carcinogenesis we used skin lesion induction by dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate in CRABP-II-knockout C57BL/6 mice. We observed earlier and more diffuse epidermal dysplasia, greater incidence and severity of tumors, reduced expression of cytokeratin 1/cytokeratin 10 and involucrin, increased proliferation, and impaired ATRA inhibition of tumor promotion compared with wild-type animals. CRABP-II-transfected HaCaT, FaDu, and A431 cells showed expression of differentiation markers, retinoic acid receptor-β/-γ signaling, ATRA sensitivity, and suppression of EGFR/v-akt murine thymoma viral oncogene homolog 1 (AKT) pathways in a fatty acid binding protein 5/peroxisome proliferator-activated receptor-β/-δ-independent manner. The opposite was true in keratinocytes isolated from CRABP-II-knockout mice. Finally, CRABP-II accumulation induced ubiquitination-associated reduction of EGFR. Our results showed reduced CRABP-II expression in human poorly differentiated squamous cell carcinomas, and its gene deletion favored experimental skin carcinogenesis and impaired ATRA antitumor efficacy, likely modulating EGFR/AKT pathways and retinoic acid receptor-β/-γ signaling. Therapeutic interventions aimed at restoring CRABP-II-mediated signaling may amplify therapeutic retinoid efficacy in nonmelanoma skin cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 136, Issue 6, June 2016, Pages 1255-1266
Journal: Journal of Investigative Dermatology - Volume 136, Issue 6, June 2016, Pages 1255-1266
نویسندگان
Daniela Passeri, Elena Doldo, Chiara Tarquini, Gaetana Costanza, Donatella Mazzaglia, Sara Agostinelli, Elena Campione, Alessandro Di Stefani, Alessandro Giunta, Luca Bianchi, Augusto Orlandi,