دورية أكاديمية
The Gα12/13 family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis
| العنوان: | The Gα12/13 family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis |
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| المؤلفون: | Martín, M.J., Tanos, T., García, A.B., Martin, D., Gutkind, J.S., Coso, O.A., Marinissen, M.J. |
| المصدر: | J. Biol. Chem. 2007;282(47):34510-34524 |
| سنة النشر: | 2007 |
| المجموعة: | Repositorio Digital Institucional - Universidad de Buenos Aires (RDI UBA) |
| مصطلحات موضوعية: | Kaposi sarcoma lesions, Oncogenic activity, Tumor growth, Tumorigenesis, Cells, Enzyme activity, Gene expression, RNA, Tumors, Proteins, G protein coupled receptor, guanine nucleotide binding protein, guanine nucleotide binding protein alpha12, guanine nucleotide binding protein alpha13, guanosine triphosphatase, heme oxygenase 1, heme oxygenase inhibitor, heterotrimeric guanine nucleotide binding protein, protoporphyrin, RhoA guanine nucleotide binding protein, short hairpin RNA, unclassified drug, vasculotropin A, chemokine receptor, Human herpesvirus 8, G protein-coupled receptor, guanine nucleotide binding protein alpha subunit, photosensitizing agent, RHOA protein, human |
| الوصف: | Heme oxygenase-1 (HO-1), an inducible enzyme that metabolizes the heme group, is highly expressed in human Kaposi sarcoma lesions. Its expression is up-regulated by the G protein-coupled receptor from the Kaposi sarcoma-associated herpes virus (vGPCR). Although recent evidence shows that HO-1 contributes to vGPCR-induced tumorigenesis and vascular endothelial growth factor (VEGF) expression, the molecular steps that link vGPCR to HO-1 remain unknown. Here we show that vGPCR induces HO-1 expression and transformation through the Gα12/13 family of heterotrimeric G proteins and the small GTPase RhoA. Targeted small hairpin RNA knockdown expression of Gα12, Gα13, or RhoA and inhibition of RhoA activity impair vGPCR-induced transformation and ho-1 promoter activity. Knockdown expression of RhoA also reduces vGPCR-induced VEFG-A secretion and blocks tumor growth in a murine allograft tumor model. NIH-3T3 cells expressing constitutively activated Gα13 or RhoA implanted in nude mice develop tumors displaying spindle-shaped cells that express HO-1 and VEGF-A, similarly to vGPCR-derived tumors. RhoAQL-induced tumor growth is reduced 80% by small hairpin RNA-mediated knockdown expression of HO-1 in the implanted cells. Likewise, inhibition of HO-1 activity by chronic administration of the HO-1 inhibitor tin protoporphyrin IX to mice reduces RhoAQL-induced tumor growth by 70%. Our study shows that vGPCR induces HO-1 expression through the Gα12/13/RhoA axes and shows for the first time a potential role for HO-1 as a therapeutic target in tumors where RhoA has oncogenic activity. ; Fil:Tanos, T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. ; Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/20.500.12110/paper_00219258_v282_n47_p34510_MartinTest; http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00219258_v282_n47_p34510_Martin_oaiTest |
| الإتاحة: | https://doi.org/20.500.12110/paper_00219258_v282_n47_p34510_MartinTest https://hdl.handle.net/20.500.12110/paper_00219258_v282_n47_p34510_MartinTest http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00219258_v282_n47_p34510_Martin_oaiTest |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/2.5/arTest |
| رقم الانضمام: | edsbas.FB1EE698 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |