کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456769 | 1548773 | 2018 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cooperation Between Pten and Smad4 in Murine Salivary Gland Tumor Formation and Progression
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کلمات کلیدی
PI3KCXPASACCHNSCCSPAYFPSGTSDCTGFβGEMMsmooth muscle actin - آکنه عضله صافImmunofluorescence - ایمونوفلورسانسTransforming growth factor β - تبدیل فاکتور رشد βSalivary gland tumor - تومور غدد بزاقیSMA - دبیرستانsalivary adenoid cystic carcinoma - سرطان آدنوئید کیستیک بزاقHead and neck squamous cell carcinomas - سرطان سلول سنگفرشی سر و گردنSalivary gland - غدد بزاقیPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازgenetically engineered mouse model - مدل موس موسوم به مهندسی ژنتیکیYellow Fluorescence Protein - پروتئین فلورسانس زردkeratin 5 - کراتین 5
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Salivary gland tumor (SGT) is a rare tumor type, which exhibits broad-spectrum phenotypic, biological, and clinical heterogeneity. Currently, the molecular mechanisms that cause SGT pathogenesis remain poorly understood. A lack of animal models that faithfully recapitulate the naturally occurring process of human SGTs has hampered research progress on this field. In this report, we developed an inducible keratin 5-driven conditional knockout mouse model to delete gene(s) of interest in murine salivary gland upon local RU486 delivery. We have deleted two major tumor suppressors, Pten, a negative regulator of the PI3K pathway, and Smad4, the central signaling mediator of TGFβ pathway, in the murine salivary gland. Our results have shown that deletion of either Pten or Smad4 in murine salivary gland resulted in pleomorphic adenomas, the most common tumor in human SGT patients. Deletion of both Pten and Smad4 in murine salivary gland developed several malignancies, with salivary adenoid cystic carcinoma (SACC) being the most frequently seen. Molecular characterization showed that SACC exhibited mTOR activation and TGFβ1 overexpression. Examination of human SGT clinical samples revealed that loss of Pten and Smad4 is common in human SACC samples, particularly in the most aggressive solid form, and is correlated with survival of SACC patients, highlighting the human relevance of the murine models. In summary, our results offer significant insight into synergistic role of Pten and Smad4 in SGT, providing a rationale for targeting mTOR and/or TGFβ signaling to control SGT formation and progression.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 20, Issue 8, August 2018, Pages 764-774
Journal: Neoplasia - Volume 20, Issue 8, August 2018, Pages 764-774
نویسندگان
Yu Cao, Han Liu, Liwei Gao, Ling Lu, Li Du, Han Bai, Jiang Li, Sherif Said, Xiao-Jing Wang, John Song, Natalie Serkova, Minjie Wei, Jing Xiao, Shi-Long Lu,