التفاصيل البيبلوغرافية
| العنوان: |
Modulatory role of phospholipase D in the activation of signal transducer and activator of transcription (STAT)-3 by thyroid oncogenic kinase RET/PTC. |
| المؤلفون: |
Young-Rae Kim1 young7403@hanmail.net, Hee Sun Byun1 bhs74@hanmail.net, Minho Won1 hoho2396@hanmail.net, Kyeong Ah Park1 silpid414@hanmail.net, Jin Man Kim2 jinmank@cnu.ac.kr, Byung Lyul Choi1 dongaam@hanmail.net, Hyunji Lee1 hjvenus@hanmail.net, Jang Hee Hong1 boniii@cnu.ac.kr, Jongsun Park1 insulin@cnu.ac.kr, Jeong Ho Seok1 jhseok@cnu.ac.kr, Dong Wook Kim3 bellocan@cnu.ac.kr, Minho Shong3 minhos@cnu.ac.kr, Seung-Kiel Park4 parksk@cnu.ac.kr, Gang Min Hur1,5 gmhur@cnu.ac.kr |
| المصدر: |
BMC Cancer. 2008, Vol. 8, Special section p1-11. 11p. 1 Color Photograph, 2 Black and White Photographs, 2 Graphs. |
| مصطلحات موضوعية: |
*PHOSPHOLIPASES, *THYROID cancer, *IMMUNOHISTOCHEMISTRY, *PHOSPHORYLATION, *BUTANOL |
| مستخلص: |
Background: RET/PTC (rearranged in transformation/papillary thyroid carcinomas) gene rearrangements are the most frequent genetic alterations identified in papillary thyroid carcinoma. Although it has been established that RET/PTC kinase plays a crucial role in intracellular signaling pathways that regulate cellular transformation, growth, and proliferation in thyroid epithelial cells, the upstream signaling that leads to the activation of RET/PTC is largely unknown. Based on the observation of high levels of PLD expression in human papillary thyroid cancer tissues, we investigated whether PLD plays a role in the regulating the RET/PTC-induced STAT3 activation. Methods: Cancer tissue samples were obtained from papillary thyroid cancer patients (n = 6). The expression level of PLD was examined using immunohistochemistry and western blotting. Direct interaction between RET/PTC and PLD was analyzed by co-immunoprecipitation assay. PLD activity was assessed by measuring the formation of [3H]phosphatidylbutanol, the product of PLDmediated transphosphatidylation, in the presence of n-butanol. The transcriptional activity of STAT3 was assessed by m67 luciferase reporter assay. Results: In human papillary thyroid cancer, the expression levels of PLD2 protein were higher than those in the corresponding paired normal tissues. PLD and RET/PTC could be coimmunoprecipitated from cells where each protein was over-expressed. In addition, the activation of PLD by pervanadate triggered phosphorylation of tyrosine 705 residue on STAT-3, and its phosphorylation was dramatically higher in TPC-1 cells (from papillary carcinoma) that have an endogenous RET/PTC1 than in ARO cells (from anaplastic carcinoma) without alteration of total STAT-3 expression. Moreover, the RET/PTC-mediated transcriptional activation of STAT-3 was synergistically increased by over-expression of PLD, whereas the PLD activity as a lipid hydrolyzing enzyme was not affected by RET/PTC. Conclusion: These findings led us to suggest that the PLD synergistically functions to activate the STAT3 signaling by interacting directly with the thyroid oncogenic kinase RET/PTC. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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