Transcript and proteome analysis reveals reduced expression of calgranulins in head and neck squamous cell carcinoma

Transcript and proteome analysis reveals reduced expression of calgranulins in head and neck squamous cell carcinoma
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DOI:
10.1016/j.ejcb.2005.01.003
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发表时间:
2005-03-01
影响因子:
6.6
通讯作者:
Bosch, FX
Bosch, FX
中科院分区:
生物学3区
文献类型:
--
作者:
Ely, MR;Nees, M;Bosch, FX

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S100和膜联蛋白家族的钙结合蛋白参与了多种重要的生理功能,包括膜重塑、钙相关的细胞内信号传导、细胞骨架动力学。组织内环境稳定和分化角质形成细胞中皮质包膜的形成。在不同类型的肿瘤和其他疾病中,这些家族成员的表达失调已被报道,但结果并不一致。本研究应用cDNA微阵列、定量逆转录聚合酶链反应(qRT-PCR)和表面增强激光解吸电离飞行时间质谱(SELDI-TOF MS)相结合的方法研究了这些基因在头颈部鳞状细胞癌(HNSCC)中的差异表达。钙颗粒蛋白A和B及膜联蛋白1和2在mRNA和蛋白水平均在HNSCC中表达下调。在通过组织芯片免疫组化验证差异基因表达后,我们检测到钙颗粒蛋白A和B在正常粘膜以及HNSCC中的新表达模式。与其中发现钙颗粒蛋白上调的皮肤鳞状细胞癌和其他癌症相反,大多数HNSCC显示出减少的和广泛紊乱的染色模式,包括不均匀的核、胞质和膜染色,甚至在肿瘤间质中的染色增强。这些结果提示粘膜中钙颗粒蛋白A和B的正常功能可能与皮肤中的不同。(c)2005年Elsevier GmbH。All rights reserved.
The calcium-binding proteins of the S100 and the annexin protein families have been implicated in a variety of important physiological functions including membrane remodeling, calcium-related Intracellular signaling, cytoskeleton dynamics. tissue homeostasis, and formation of the cornified envelope in differentiating keratinocytes. Deregulated expression of members of these families has been reported in different types of neoplasia and other diseases, but the results were not consistent. Here we have applied a combination of cDNA microarrays, quantitative reverse transcriptase-PCR (qRT-PCR) and surface enhanced laser desorption ionisation-time of flight mass spectrometry (SELDI-TOF MS) to Study differential expression of these genes in head and neck squamous cell carcinoma (HNSCC). The calgranulins A and B and annexins 1 and 2 were found to be down-regulated in HNSCC, compared with normal mucosa, at both the mRNA and protein level. Upon validation of the differential gene expression by tissue microarray immunohistochemistry, we detected novel expression patterns of calgranulins A and B both in normal mucosa as well as in HNSCC. In contrast to squamous cancer of skin and other cancers in which the calgranulins were found to be up-regulated, most HNSCC showed reduced and widely deranged staining patterns including heterogeneous nuclear, cytoplasmic and membranous staining, and even enhanced staining in the tumor stroma. These observations suggest that the normal function of the calgranulins A and B in mucosa might be different from that in skin. (c) 2005 Elsevier GmbH. All rights reserved.