期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 24, 期 4, 页码 643-655出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1755-148X.2011.00869.x
关键词
integrin; Sp1; NFI; AP-1; alpha 5; uveal melanoma; promoter
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- 'Fonds de la Recherche en Sante du Quebec' (FRSQ)
- Canadian Institutes of Health Research (CIHR)
- Canadian National Institute for the Blind (CNIB)
Cancer aggressiveness is related to the ability of cancer cells to escape the anchorage dependency toward the extracellular matrix, a process regulated by the integrin alpha 5 beta 1 and its ligand fibronectin. Here, we characterized the expression of the alpha 5 gene in human uveal melanoma cell lines with distinct tumorigenic properties and investigated some of the mechanisms underlying the variations of their malignancy. Strong and weak expression of alpha 5 was observed in cells with no (T108/T115) and high (T97/T98) tumorigenic properties, respectively. Expression and DNA binding of the transcription factors Sp1, activator protein 1 (AP-1) (both acting as activators), and nuclear factor I (NFI) (a strong repressor) to the alpha 5 promoter were demonstrated in all cell lines. A reduced expression of AP-1 combined with a dramatic increase in NFI correlated with the suppression of alpha 5 expression in T97 and T98 cells. Restoring alpha 5 expression in T97 cells entirely abolished their tumorigenicity in immunodeficient mice. These uveal melanoma cell lines might therefore prove particularly useful as cellular models to investigate alpha 5 beta 1 function in the pathogenesis of invasive uveal melanoma.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据