ASSOCIATION OF ELEVATED PROTEIN-KINASE CK2 ACTIVITY WITH AGGRESSIVE-BEHAVIOR OF SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK
ASSOCIATION OF ELEVATED PROTEIN-KINASE CK2 ACTIVITY WITH AGGRESSIVE-BEHAVIOR OF SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK
复制标题
DOI：
10.1007/bf03401606
复制
发表时间：
1995-09-01
影响因子：
5.7
通讯作者：
AHMED, K
中科院分区：
文献类型：
--
作者：
GAPANY, M;FAUST, RA;AHMED, K
背景：蛋白激酶CK2（也称为酪蛋白激酶2）是一种广泛分布于真核生物中的非信使蛋白丝氨酸/苏氨酸激酶。已发现 CK2 可以磷酸化多种胞质和核底物，这些底物与 DNA、RNA 和蛋白质合成和分化的调节密切相关。因此，我们提出了这样的假设：上呼吸消化道粘膜恶性转化为头颈鳞状细胞癌 (SCCHN) 可能与 CK2 活性改变有关。 材料和方法：为此，我们对 SCCHN 肿瘤和正常口咽粘膜的手术标本进行亚细胞分离。然后，我们使用 CK2 特异性肽底物 (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu) 定量这些样本的细胞质和细胞核中的 CK2 活性。结果：我们发现，相对于正常口咽粘膜，SCCHN 肿瘤的细胞核（p < 0.0005）和细胞质（p < 0.0034）区室中的 CK2 活性显着升高。此外，SCCHN 肿瘤细胞胞浆部分中的 CK2 活性与分化程度较低的组织学分级 (p < 0.037)、阳性淋巴结转移状态 (p < 0.056) 和不良临床结果 (p < 0.028) 相关。 Kaplan-Meier 累积生存分析显示，高 CK2 活性患者组的生存率大大降低，具有很高的统计显着性 (p < 0.023)。结论：这些初步数据表明，上呼吸消化道粘膜的恶性转化与 CK2 活性的改变有关。结果进一步表明，这种蛋白激酶的失调可能在 SCCHN 的病理学中发挥重要作用，并且 CK2 活性可能是这种恶性肿瘤的预后指标。
Background: Protein kinase CK2 (also known as casein kinase 2) is a messenger-independent protein serine/ threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein syn thesis, and differentiation. We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity.Materials and Methods: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu). Results: We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023).Conclusions: These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.