کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8956336 1646147 2018 30 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pituitary somatolactotropes evade an oncogenic response to Ras
ترجمه فارسی عنوان
سموتولاکتوتروپ های هیپوفیز از واکنش آن کوهی به راس فرار می کنند
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
چکیده انگلیسی
Distinct cell types have been shown to respond to activated Ras signaling in a cell-specific manner. In contrast to its pro-tumorigenic role in some human epithelial cancers, oncogenic Ras triggers differentiation of pheochromocytoma cells and medullary thyroid carcinoma cells. Furthermore, we have previously demonstrated that in pituitary somatolactotropes, activated Ras promotes differentiation and is not sufficient to drive tumorigenesis. These findings demonstrate that lactotrope cells have the ability to evade the tumorigenic fate that is often associated with persistent activation of Ras/ERK signaling, and suggest that there may be differential expression of inhibitory signaling molecules or negative cell cycle regulators that act as a brake to prevent the tumorigenic effects of sustained Ras signaling. Here we aim to gain further insight into the mechanisms that allow GH4T2 cells to evade an oncogenic response to Ras. We show that Ral, but likely not menin, plays a key role in directing Ras-mediated differentiation of somatolactotropes, which may allow these cells to escape the tumorigenic fate that is often associated with activated Ras signaling. We also show that dominant negative Ras expression results in reduced GH4T2 cell proliferation and transformation, but does not influence differentiation. Taken together, the data presented here begin to shed light on the mechanisms by which pituitary somatolactotropes evade an oncogenic response to persistently activated Ras signaling and suggest that the architecture of the Ras signaling cascade in some endocrine cell types may be distinct from that of cells that respond to Ras in an oncogenic manner.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 476, 15 November 2018, Pages 165-172
نویسندگان
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