کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151363 | 1089986 | 2012 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Proprotein Convertase Subtilisin/Kexin Type 9 Deficiency Reduces Melanoma Metastasis in Liver
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کلمات کلیدی
TNFαPCSK9LDLcTRAF2LDLRHCDBcl-2qPCRNF-κBLPDs - LPD هاtumor necrosis factor-α - تومور نکروز عامل αhigh cholesterol diet - رژیم غذایی کلسترول بالاlipoprotein-deficient serum - سرم کمبود لیپوپروتئینTNF receptor-associated factor 2 - عامل گیرنده TNF 2B-cell lymphoma 2 - لنفوم سلول B 2wild type - نوع وحشیquantitative polymerase chain reaction - واکنش زنجیره ای پلیمراز کمیProprotein convertase subtilisin/kexin type 9 - پروتیکین تبدیل اساتید سوتیلیسین / نوع ککسین 9total cholesterol - کلسترول تامLow-density lipoprotein cholesterol - کلسترول لیپوپروتئین با چگالی کمLow-density lipoprotein receptor - گیرنده لیپوپروتئین با چگالی کم
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Proprotein Convertase Subtilisin/Kexin Type 9 Deficiency Reduces Melanoma Metastasis in Liver Proprotein Convertase Subtilisin/Kexin Type 9 Deficiency Reduces Melanoma Metastasis in Liver](/preview/png/2151363.png)
چکیده انگلیسی
High circulating cholesterol is associated with hypercholesterolemia, atherosclerosis, and stroke. However, the relation between cholesterol and tumorigenesis/metastasis is controversial. The proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein cholesterol homeostasis by targeting the low-density lipoprotein receptor (LDLR) for degradation. PCSK9 is mostly expressed in liver, which is one of the most common sites for metastatic disease. To reveal the function of PCSK9 and also evaluate the impact of cholesterol in liver metastasis development, B16F1 melanoma cells were injected into wild-type (WT) and Pcsk9-/- mice to induce liver metastasis. On chow diet, Pcsk9-/- mice harbored two-fold less liver metastases than WT mice. This decrease is related to low cholesterol levels in Pcsk9-/- mice, as the protection was lost after normalizing Pcsk9-/- cholesterol levels by a 2-week high cholesterol diet. Furthermore, a prolongation of this diet strongly increased metastasis in both genotypes, suggesting that high cholesterol levels promote metastatic progression. The protective effect of the PCSK9 deficiency is also associated with increased apoptosis in liver stroma and metastases. Tumor necrosis factor.α (TNFα) mRNA and protein were, respectively, higher in liver stroma and plasma of injected mice, likely increasing the apoptotic TNFα signaling. Furthermore, the anti-apoptotic factor B-cell lymphoma 2 was downregulated. TNFα regulation is LDLR-independent, as its mRNA level was similarly upregulated in mice lacking both PCSK9 and LDLR. Our findings show that PCSK9 deficiency reduces liver metastasis by its ability to lower cholesterol levels and by possibly enhancing TNFα-mediated apoptosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 14, Issue 12, December 2012, Pages 1122-1131, IN2-IN5
Journal: Neoplasia - Volume 14, Issue 12, December 2012, Pages 1122-1131, IN2-IN5
نویسندگان
Xiaowei Sun, Rachid Essalmani, Robert Day, Abdel M. Khatib, Nabil G. Seidah, Annik Prat,