مورد إلكتروني
Inhibition of oncogene-induced inflammatory chemokines using a farnesyltransferase inhibitor.
| العنوان: | Inhibition of oncogene-induced inflammatory chemokines using a farnesyltransferase inhibitor. |
|---|---|
| المصدر: | Department of Microbiology and Immunology Faculty Papers |
| بيانات النشر: | Jefferson Digital Commons 2008-01-01T08:00:00Z |
| تفاصيل مُضافة: | Degeorge, Katharine C Degeorge, Brent R Testa, James S Rothstein, Jay L |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | BACKGROUND: Farnesyltransferase inhibitors (FTI) are small molecule agents originally formulated to inhibit the oncogenic functions of Ras. Although subsequent analysis of FTI activity revealed wider effects on other pathways, the drug has been demonstrated to reduce Ras signaling by direct measurements. The purpose of the current study was to determine if FTI could be used to inhibit the inflammatory activities of a known Ras-activating human oncoprotein, RET/PTC3. RET/PTC3 is a fusion oncoprotein expressed in the thyroid epithelium of patients afflicted with thyroid autoimmune disease and/or differentiated thyroid carcinoma. Previous studies have demonstrated that RET/PTC3 signals through Ras and can provoke nuclear translocation of NFkappaB and the downstream release of pro-inflammatory mediators from thyroid follicular cells in vitro and in vivo, making it an ideal target for studies using FTI. METHODS: For the studies described here, an in vitro assay was developed to measure FTI inhibition of RET/PTC3 pro-inflammatory effects. Rat thyrocytes transfected with RET/PTC3 or vector control cDNA were co-cultured with FTI and examined for inhibition of chemokine expression and secretion measured by RT-PCR and ELISA. Immunoblot analysis was used to confirm the level at which FTI acts on RET/PTC3-expressing cells, and Annexin V/PI staining of cells was used to assess cell death in RET/PTC3-expressing cells co-cultured with FTI. RESULTS: These analyses revealed significant mRNA and protein inhibition of chemokines Ccl2 and Cxcl1 with nanomolar doses of FTI. Neither RET/PTC3 protein expression nor apoptosis were affected at any dose of FTI investigated. CONCLUSION: These data suggest that FTI may be applied as an effective inhibitor for RET/PTC3-oncogene induced pro-inflammatory mediators. |
| مصطلحات الفهرس: | Thomas Jefferson University, Kimmel Cancer Institute, Department of Immuology and Microbiology, Otolaryngology-Head and Neck Surgery, Center for Translational Medicine, Department of Medicine, Department of Microbiology and Immunology, chemokine, complementary DNA, immunoglobulin enhancer binding protein, lipocortin 5, oncoprotein, protein farnesyltransferase inhibitor, animal cell, animal experiment, apoptosis, article, autoimmune thyroiditis, cell culture, cell death, enzyme linked immunosorbent assay, genetic transfection, immunoblotting, in vitro study, in vivo study, nonhuman, oncogene, protein expression, protein secretion, rat, real time polymerase chain reaction, thyroid carcinoma, thyroid cell, thyroid follicle cell, vector control, Biological Phenomena, Cell Phenomena, and Immunity, Medical Genetics, article |
| URL: | |
| الإتاحة: | Open access content. Open access content |
| ملاحظة: | application/pdf |
| أرقام أخرى: | TVJ oai:jdc.jefferson.edu:mifp-1007 704077089 |
| المصدر المساهم: | THOMAS JEFFERSON UNIV From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.ocn704077089 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |