High expression levels of nuclear factor kappa B and gelatinases in the tumorigenesis of oral squamous cell carcinoma
High expression levels of nuclear factor kappa B and gelatinases in the tumorigenesis of oral squamous cell carcinoma
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DOI：
10.1002/hed.20437
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发表时间：
2006-10-01
影响因子：
2.9
通讯作者：
Pillai, M. Radhakrishna
中科院分区：
文献类型：
--
作者：
Bindhu, O. S.;Ramadas, K.;Pillai, M. Radhakrishna
背景癌前病变/潜在恶性口腔病变转化为恶性病变的细胞机制尚不清楚。已有研究表明基质金属蛋白酶（MMP）过度表达与头颈部鳞状细胞癌（HNSCC）的发生、发展有直接关系。在不同癌症中观察到的MMP活化，特别是MMP 2和MMP 9，已显示通过转录因子核因子κ B（NF-κ B）介导。本研究分析了明胶酶和NF-κ B B在人类口腔肿瘤进展的不同组织学阶段的临床意义。方法学包括NF-κ B和I κ B α（抑制剂κ B α）的MMP 2、MMP 9、p50和p65组分的免疫组织化学。进行明胶酶谱分析以确定明胶分解活性的程度。Western blotting检测酶谱中的明胶酶带，电泳迁移率变动分析（EMSA）检测NF-κ B的活化。明胶酶的表达和明胶分解活性的强度随着恶性肿瘤的组织学进展而逐渐增加。这一发现支持了在癌前病变和浸润性癌之间发生肿瘤浸润的组织学证据。NF-κ B（p50-p65形式）的核转位逐渐通过口腔组织的癌前阶段进展到侵袭阶段，表明NF-κ B在口腔肿瘤发生过程中活化。NF-κ B活化与明胶酶表达模式相关。这项研究的结果表明，NF-κ B B在口腔粘膜恶性转化过程中对明胶酶的活化具有调节作用。(c)2006 Wiley Periodicals，Inc.
Background. The cellular mechanisms involved in transformation of a premalignant/potentially malignant oral lesion to a malignant one remain unclear. Previous studies have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). MMP activation, particularly MMP2 and MMP9, observed in different cancers, has been shown to be mediated via the transcription factor nuclear factor kappa B (NF-kappa B). The present study analyzes the clinical significance of gelatinases and NF-kappa B in various histologic phases of human oral tumor progression.Methods. Methodology included immunohistochemistry for MMP2, MMP9, p50, and p65 components of NF-kappa B and I kappa B alpha (inhibitor kappa B alpha). Gelatin zymography was carried out to determine the extent of gelatinolytic activity. Western blotting was used to confirm the gelatinolytic bands of zymogram, and electrophoretic mobility shift assay (EMSA) was carried out to confirm NF-kappa B activation.Results. A gradual increase was evident in the intensity of the expression and gelatinolytic activity of gelatinase paralleling the histologic progression of malignancy. This finding supports the histologic evidence of tumor invasion occurring in the transition between premalignancy and invasive cancer. Nuclear translocation of NF-kappa B (p50-p65 form) gradually progresses through the premalignant phase of oral tissue to the invasive phase, showing NF-kappa B activation during oral tumorigenesis. NF-kappa B activation correlatively paralleled the pattern of expression of gelatinases.Conclusions. The results of this study suggest a regulatory role for NF-kappa B on activation of gelatinases during malignant transformation in the oral mucosa. (c) 2006 Wiley Periodicals, Inc.