کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10915438 | 1090060 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Active p21-Activated Kinase 1 Rescues MCF10A Breast Epithelial Cells from Undergoing Anoikis
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کلمات کلیدی
ECMEGFGPCRPARPPAKLPAlysophosphatidic acid - اسید لیسفسفیدیدCell survival - بقای سلولیApoptosis - خزان یاختهایepidermal growth factor - عامل رشد اپیدرمیPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازCaspase activation - فعال شدن کاسپازExtracellular matrix - ماتریکس خارج سلولیhemagglutinin - هماگلوتینینprotein kinases - پروتئین کینازPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازbreast carcinoma - کارسینوم سینه، کارسینوم پستانp21-activated kinase - کیناز فعال p21
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The protein kinase, PAKi, is overexpressed in human breast cancer and may contribute to malignancy through induction of proliferation and invasiveness. In this study, we examined the role of PAKi in the survival of detached MCF10A breast epithelial cells to test whether it may also regulate the early stages of neoplasia. MCF10A cells undergo anoikis, as measured by the cleavage of caspase 3 and poly(ADPribose) polymerase (PARP), after more than 8 hours of detachment. Endogenous Akt, PAKi, BAD are phosphorylated in attached MCF10A cells, but these phosphorylation events are all lost during the first 8 hours of detachment. Expression of constitutively active PAKi or Akt suppresses the cleavage of caspase 3 and PARP in detached MCF10A cells. Cooverexpression of active PAKi with dominant-negative Akt, or of active Akt with dominant-negative PAKi, still suppresses anoikis. Thus, Akt and PAKi enhance survival through pathways that are at least partially independent. PAKi-dependent regulation of anoikis is likely to occur early in the apoptotic cascade as expression of dominant-negative PAKi increased the cleavage of the upstream caspase 9, while constitutively active PAKi inhibited caspase 9 activation. These results support a role for activated PAKi in the suppression of anoikis in MCF10A epithelial cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 7, Issue 7, July 2005, Pages 638-645
Journal: Neoplasia - Volume 7, Issue 7, July 2005, Pages 638-645
نویسندگان
Raymond E. Menard, Andrew P. Jovanovski, Raymond R. Mattingly,