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The role of the Epstein-Barr virus l...
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Scholle, Frank.
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The role of the Epstein-Barr virus latent membrane protein 2A in epithelial cells.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
The role of the Epstein-Barr virus latent membrane protein 2A in epithelial cells./
作者:
Scholle, Frank.
面頁冊數:
171 p.
附註:
Source: Dissertation Abstracts International, Volume: 61-07, Section: B, page: 3411.
Contained By:
Dissertation Abstracts International61-07B.
標題:
Biology, Microbiology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9979487
ISBN:
0599855339
The role of the Epstein-Barr virus latent membrane protein 2A in epithelial cells.
Scholle, Frank.
The role of the Epstein-Barr virus latent membrane protein 2A in epithelial cells.
- 171 p.
Source: Dissertation Abstracts International, Volume: 61-07, Section: B, page: 3411.
Thesis (Ph.D.)--The University of North Carolina at Chapel Hill, 2000.
The Epstein-Barr virus latent membrane protein 2A contributes to the maintenance of viral latency in infected B lymphocytes. Signal transduction cascades which originate from the B cell receptor complex are inhibited by LMP2A, preventing the expression of EBV immediate-early genes and viral reactivation from latency. While LMP2A is consistently detected in nasopharyngeal carcinoma, an epithelial cell malignancy, its function in this cell type is not understood. In this study, the interaction of LMP2A with epithelial cell signaling pathways was investigated and the effects of LMP2A expression in this cell type were determined. LMP2A is associated with protein kinase activities in epithelial cells and is phosphorylated in adherent cells. Tyrosine phosphorylation of LMP2A in epithelial cells is induced by cell adhesion to the extracellular matrix. While LMP2A is phosphorylated by Src kinases in B lymphocytes, this was found not to be the case in epithelial cells. Instead, a negative Src regulator, the protein kinase Csk, induced LMP2A phosphorylation in an adhesion-dependent manner. Investigation of LMP2A phosphorylation patterns detected differences in vitro and in vivo and between epithelial cells and B lymphocytes. LMP2A was expressed in an immortalized human keratinocyte cell line, HaCaT and its effects on epithelial cell behavior were determined in organotypic raft culture. LMP2A induced hyperproliferation and inhibited HaCaT cell differentiation in this system. LMP2Aexpressing HaCaT cells were able to grow in soft agar and formed aggressive tumors in nude mice, which developed lymph node metastases in 55% of the animals. Compared to tumors arising with parental HaCaT cells and vector control cells, the LMP2A tumors were poorly differentiated, well vascularized, and highly proliferative. Some of these effects were due at least in part to activation of the phosphatidylinositol-3<super>′</super>-kinase (PI3-kinase) signaling pathway and its downstream component Akt. Inhibition of PI3-kinase blocked colony formation in soft agar.
ISBN: 0599855339Subjects--Topical Terms:
1017734
Biology, Microbiology.
The role of the Epstein-Barr virus latent membrane protein 2A in epithelial cells.
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The Epstein-Barr virus latent membrane protein 2A contributes to the maintenance of viral latency in infected B lymphocytes. Signal transduction cascades which originate from the B cell receptor complex are inhibited by LMP2A, preventing the expression of EBV immediate-early genes and viral reactivation from latency. While LMP2A is consistently detected in nasopharyngeal carcinoma, an epithelial cell malignancy, its function in this cell type is not understood. In this study, the interaction of LMP2A with epithelial cell signaling pathways was investigated and the effects of LMP2A expression in this cell type were determined. LMP2A is associated with protein kinase activities in epithelial cells and is phosphorylated in adherent cells. Tyrosine phosphorylation of LMP2A in epithelial cells is induced by cell adhesion to the extracellular matrix. While LMP2A is phosphorylated by Src kinases in B lymphocytes, this was found not to be the case in epithelial cells. Instead, a negative Src regulator, the protein kinase Csk, induced LMP2A phosphorylation in an adhesion-dependent manner. Investigation of LMP2A phosphorylation patterns detected differences in vitro and in vivo and between epithelial cells and B lymphocytes. LMP2A was expressed in an immortalized human keratinocyte cell line, HaCaT and its effects on epithelial cell behavior were determined in organotypic raft culture. LMP2A induced hyperproliferation and inhibited HaCaT cell differentiation in this system. LMP2Aexpressing HaCaT cells were able to grow in soft agar and formed aggressive tumors in nude mice, which developed lymph node metastases in 55% of the animals. Compared to tumors arising with parental HaCaT cells and vector control cells, the LMP2A tumors were poorly differentiated, well vascularized, and highly proliferative. Some of these effects were due at least in part to activation of the phosphatidylinositol-3<super>′</super>-kinase (PI3-kinase) signaling pathway and its downstream component Akt. Inhibition of PI3-kinase blocked colony formation in soft agar.
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