Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis
Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis
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DOI：
10.1038/sj.onc.1203104
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发表时间：
1999-12-09
期刊：
影响因子：
8
通讯作者：
Jorcano, JL
中科院分区：
文献类型：
--
作者：
Budunova, IV;Perez, P;Jorcano, JL
为了阐明NF-κ B B在小鼠皮肤癌发生中的可能作用，我们研究了p50（NF-κ B1）、p52（NF-κ B2）、p65（ReIA）和I κ B-α抑制剂的表达以及κ B结合活性在成年SENCAR小鼠皮肤、皮肤乳头状瘤和鳞状细胞癌（SCC）中的表达。我们发现，在正常表皮中，上述蛋白质主要表达于基底细胞的胞质中。Western blot分析显示，小鼠皮肤肿瘤中p50和p52的表达从促进中期开始急剧增加。我们还发现许多晚期乳头状瘤和表皮中I κ B-α蛋白的水平低于正常表皮。EMSA结果显示小鼠皮肤肿瘤中κ B结合活性增加，提示p50是正常表皮和肿瘤中组成性κ B结合复合物的主要成分。已经显示，核I κ B蛋白Bcl-3能够增加p50/p50同二聚体与小鼠胸腺细胞中不同κ B位点的结合。我们发现Bcl-3在晚期乳头状瘤和SCC中的过度表达可以解释小鼠皮肤肿瘤中p50相关的kappa B结合的选择性增加，因此，我们的结果强烈提示p50在皮肤癌发生中的重要作用。
To elucidate the possible role of NF-kappa B in mouse skin carcinogenesis we studied the expression of p50 (NF-kappa B1), p52 (NF-kappa B2), p65 (ReIA) and I kappa B-alpha inhibitor as well as kappa B-binding activity in adult SENCAR mouse skin, skin papillomas, and squamous cell carcinomas (SCC) generated by a two-stage carcinogenesis protocol. We found that in normal epidermis all of the above proteins were mostly expressed in the cytoplasm of basal cells. Western blot analysis revealed a dramatic increase of p50 and p52 expression in mouse skin tumors starting from the middle stage of promotion. We also found that the level of I kappa B-alpha protein in many late papillomas and see was lower than in normal epidermis, Results of EMSA showed an increase in kappa B-binding activity in mouse skin tumors and suggested that p50 is the major component of constitutive kappa B-binding complexes in normal epidermis and in tumors. It has been shown that nuclear I kappa B protein Bcl-3 is able to increase p50/p50 homodimer binding to the different kappa B sites in mouse thymocytes. Our finding on Bcl-3 overexpression in late papillomas and SCC could explain the selective increase of p50-related kappa B-binding in mouse skin tumors, Thus, our results strongly suggest the important role of p50 in skin carcinogenesis.