Cancer Research Institute, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russian Federation.
J Cancer Res Clin Oncol. 2013 Apr;139(4):625-33. doi: 10.1007/s00432-012-1366-0. Epub 2012 Dec 27.
The transcription factors NF-kB, HIF-1 and vascular endothelial growth factors (VEGF) are known to play an important role in pathogenesis of squamous cell carcinoma of head and neck (SCCHN).
The aim of the study was to determine the NF-kB, HIF-1 and VEGF, expression their characteristics in squamous cell carcinoma of head and neck.
Transcription factors and VEGF expression were measured by ELISA kits. Proteasome and calpain activity were determined using specific fluorogenic substrate. Proteasome subunits composition was measured by Western blot analysis.
In the present study, we revealed the connection between SCCHN lymphogenous metastasis development and NF-kB p50 expression. An increase in total, 26S and 20S proteasome activities and calpain activity was observed in cancer tissues in comparison with agreed standard (non-transformed tissue). The dynamics of changes in proteasome activity and proteasome subunits content during lymph nodes metastasis development had a complex pattern. Nonparametric analysis of variance showed the connection between the extent of metastatic affection of regional lymph nodes, total proteasome activity and LMP2 expression. Proteasome and calpain systems corresponded and interacted with each other. We also revealed a positive correlation between the NF-kB p65 and p50 expression and proteasome activity.
Taken together, our results suggest that above mentioned transcription factors and intracellular proteolytic systems are involved in SCCHN progression and metastasis. Moreover, the opportunity of transcription factors regulation by proteasome takes place in oncogenesis of SCCHN. The results provide a basis for new prognostic tests and development of novel targeted therapy.
转录因子 NF-kB、HIF-1 和血管内皮生长因子 (VEGF) 已被证实在头颈部鳞状细胞癌 (SCCHN) 的发病机制中发挥重要作用。
本研究旨在确定 NF-kB、HIF-1 和 VEGF 的表达及其在头颈部鳞状细胞癌中的特征。
通过 ELISA 试剂盒测定转录因子和 VEGF 的表达。使用特异性荧光底物测定蛋白酶体和钙蛋白酶的活性。通过 Western blot 分析测定蛋白酶体亚基组成。
在本研究中，我们揭示了 SCCHN 淋巴转移发展与 NF-kB p50 表达之间的联系。与公认的标准（未转化的组织）相比，在癌组织中观察到总蛋白酶体、26S 和 20S 蛋白酶体活性以及钙蛋白酶活性增加。在淋巴结转移发展过程中，蛋白酶体活性和蛋白酶体亚基含量变化的动态具有复杂的模式。非参数方差分析显示，区域淋巴结转移受累程度、总蛋白酶体活性和 LMP2 表达之间存在联系。蛋白酶体和钙蛋白酶系统相互对应并相互作用。我们还发现 NF-kB p65 和 p50 表达与蛋白酶体活性之间存在正相关。
综上所述，我们的结果表明，上述转录因子和细胞内蛋白水解系统参与了 SCCHN 的进展和转移。此外，转录因子通过蛋白酶体进行调节的机会发生在 SCCHN 的发生过程中。这些结果为新的预后检测和新型靶向治疗的发展提供了依据。
