- 作者: Chang-Yao Hsigh; Chi-An Chen; Chia-Hung Chou; Kuo-Pao Lai; Yung-Ming Jeng; Min-Liang Kuo; Lin-Hung Wei
- 作者服務機構: Departments of Oncology, Obstetrics Gynecology, Pathology, National Taiwan Univrsity Hospital and National Taiwan University College of Medicine, and Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology, National Taiwan University College of Medicine, Taipei , Taiwan, ROC
- 中文摘要: --
- 英文摘要: Vascular endothelial growth factor C (VEGF-C)is animportant growth factor that governs lymphatic spreadand the development of intraperitoneal tumors associat-ed with epithelial ovarian cancer; however, its regulationis not yet understood.Overexpression of Her-2/neu isrelated to poor survival in advanced epithelial ovariancarcinoma patients. Accordingly, this study attempted toanalyze the association between the Her-2/neu oncogeneand VEGF-C in ovarian carcinoma and to elucidate themolecular mechanism of VEGF-C induction by Her-2/neu. Immunohistochemistry was used to determine theexpression of Her-2/neu and VEGF-C in tissues from41 patients with epithelial ovarian carcinoma. SeveralHer-2/neu-stably-transfected Caov-3 ovarian carcinomacells were used to evaluate the effect of Her-2/neu onVEGF-C, the possible regulation mechanism,and thebiological function of VEGF-C.Our experimental resultsidentified a significant association between the Her-2/neu oncogene and VEGF-C expression in both epithelialovarian cancer patients(p<0.05; Fisher's exact test) andin vitro cell lines.The overexpression of Her-2/neu inCaov-3 ovarian cancer cells resulted in induction of aconsiderable amount of VEGF-C mRNA and protein;thisprocess was dose-dependently inhibited by herceptin.The generation of VEGF-C significantly increased endo-thelial permeability. Pharmacological and genetic inhibi-tion assays revealed that the cytoplasmic signaling mol-ecule, p38 MAPK, and the transcriptional factor, NF-KB,are critically involved in the transcriptional activation ofthe VEGF-C gene by Her-2/neu. In conclusion,this workclearly establishes that the Her-2/neu oncogene is essen-tial for the regulation of VEGF-C in ovarian carcinoma.Itmay be possible to use the monoclonal antibody target-ing Her-2/neu receptor to limit the formation of malig-nant ascites and lymphatic spread in ovarian carcinoma.
- 中文關鍵字: --
- 英文關鍵字: --