کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151465 | 1089995 | 2012 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of Proprotein Convertases in Prostate Cancer Progression
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کلمات کلیدی
FBSPSARPMIMVDEGF(R)Microvessel density - تراکم Microvesselfetal bovine serum - سرم جنین گاوepidermal growth factor (receptor) - عامل رشد اپیدرمی (گیرنده)Non-target - غیر هدفRoswell Park Memorial Institute medium - موسسه خاطرات Roswell Park mediumprostate-specific antigen - پادگن مخصوص پروستاتproprotein convertase - پروپروتئین تبدیل کننده
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Better understanding of the distinct and redundant functions of the proprotein convertase (PC) enzyme family within pathophysiological states has a great importance for potential therapeutic strategies. In this study, we investigated the functional redundancy of PCs in prostate cancer in the commonly used androgen-sensitive LNCaP and the androgen-independent DU145 human cell lines. Using a lentiviral-based shRNA delivery system, we examined in vitro and in vivo cell proliferation characteristics of knockdown cell lines for the endogenous PCs furin, PACE4, and PC7 in both cell lines. Of the three PCs, only PACE4 was essential to maintain a high-proliferative status, as determined in vitro using XTT proliferation assays and in vivo using tumor xenografts in nude mice. Furin knockdowns in both cell lines had no effects on cell proliferation or tumor xenograft growth. Paradoxically, PC7 knockdowns reduced in vitro cellular proliferation but had no effect in vivo. Because PCs act within secretion pathways, we showed that conditioned media derived from PACE4 knockdown cells had very poor cell growth-stimulating effects in vitro. Immunohistochemistry of PACE4 knockdown tumors revealed reduced Ki67 and higher p27KIP levels (proliferation and cell cycle arrest markers, respectively). Interestingly, we determined that the epidermal growth factor receptor signaling pathway was activated in PC7 knockdown tumors only, providing some explanations of the paradoxical effects of PC7 silencing in prostate cancer cell lines. We conclude that PACE4 has a distinct role in maintaining proliferation and tumor progression in prostate cancer and this positions PACE4 as a relevant therapeutic target for this disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 14, Issue 11, November 2012, Pages 1032-1042, IN4-IN6
Journal: Neoplasia - Volume 14, Issue 11, November 2012, Pages 1032-1042, IN4-IN6
نویسندگان
Frédéric Couture, François D'Anjou, Roxane Desjardins, François Boudreau, Robert Day,