Expression of Caveolin-1 and its impact on clinical behavior of nasopharyngeal carcinoma patients
Date Issued
2007
Date
2007
Author(s)
Wang, Ying-Piao
DOI
en-US
Abstract
Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma occurring in the epithelial lining of the nasopharynx. The incidence is high in Southeast China, Hong Kong and Taiwan, however it is rare in western countries indicating a remarkably distinctive ethnic and geographic distribution that differing from other head and neck cancers. The tumorgenesis of NPC is a multi-factorial process, including genetic, environmental and Epstein-Barr virus. Latent membrane protein 1(LMP-1) and Latent membrane protein 2A (LMP2A) are EBV-encoded proteins expressed during latent phase, and transcripts are detected in 65% and 95% of the tumors respectively. It has been demonstrated EBV-encoded LMP-1 can cause cellular transformation, and LMP2A transforms epithelial cells, inhibits cell differentiation through activating PI3-kinase-Akt pathway. Interesting, both LMP-1 and LMP2A is targeted to lipid rafts/caveolae. Caveolin-1, an essential protein constituent of caveolae can modulate Akt signaling pathway and enhances cell survival. Caveolin-1 was over-expressed on bladder cancer, prostate cancer, esophageal cancer and thyroid papillary carcinoma. The aim of this study is to investigate the expression of caveolin-1 on NPC and its impacts on clinical manifestations of NPC patients. The effect of caveolin-1 on Akt signaling in NPC-TW01 cells will be elucidated in this study.
The expression of caveolin-1 was investigated in 74 NPC specimens, 29 control tissues and some cell lines. Our data revealed the caveolin-1 is over-expressed at transcription level in NPC patients (P=0.0002). Late-stage NPC (stage III, IV) patients have higher level of caveolin-1 expression than early-stage (stage I,II) ones (P=0.0002). After multiple regression analysis, three factors including tumor staging, tumor size (T) and lymph node metastasis (N) are included in the model with significant difference. The overall survival rate is poor in patients with high level of caveolin-1 expression (Log-rank test, P=0.03). Over-expressed caveolin-1 in TW01 cells increased more than 50% phosphorylated Akt protein intensity. Knockdown of caveolin-1 by four shRNAs substantially reduced Akt protein levels and almost abolished phosphorylated Akt protein compared with that in untreated TW01 and empty vector control cells. It suggested caveolin-1 may modulate Akt signaling in NPC TW01 cell lines.
Subjects
鼻咽癌
Caveolin-1
臨床分期
Akt
NPC
Staging
SDGs
Type
text
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