Constitutive expression of NF-kappa B is a characteristic feature of mycosis fungoides: implications for apoptosis resistance and pathogenesis.
Constitutive expression of NF-kappa B is a characteristic feature of mycosis fungoides: implications for apoptosis resistance and pathogenesis.
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NF-κ B 的组成型表达是蕈样肉芽肿的一个特征：对细胞凋亡抵抗和发病机制的影响。
作者：
K. Izban;Melek Ergin;J. Qin;R. L. Martínez;R. Pooley;S. Saeed;S. Alkan
NF-κ B家族转录因子是炎症反应、免疫球蛋白（IG）类别转换、细胞分化和凋亡过程中表达的基因的重要调节因子。最近，NF-κ B家族的成员，包括p65（Rel A），已经涉及促进各种造血肿瘤的存活，包括T细胞恶性肿瘤，如成人T细胞白血病-淋巴瘤。我们研究了蕈样肉芽肿（MF）中活性NF-κ B p65（Rel A）的表达以及NF-κ B化学抑制剂对皮肤T细胞淋巴瘤（CTCL）细胞系凋亡的影响。通过使用检测p65（Rel A）的活化形式的单克隆小鼠抗体，对来自23个皮肤病变的石蜡包埋组织和来自诊断为MF的患者的单个淋巴结活检组织的p65（Rel A）表达进行评价。在CTCL细胞系HuT-78和HH中，通过碘化丙啶（PI）/细胞周期分析检测亚二倍体（sub-G（0））群体和通过测定增加的膜联蛋白V/7-氨基-放线菌素D（7-AAD）表达，定量测定了NF-κ B抑制剂胶毒蛋白MG 132、BAY 11-7082和BAY 11-7085处理后的细胞凋亡。通过电泳迁移率变动分析（EMSA）和定量光密度法分析化学抑制前后CTCL细胞核提取物的NF-κ B核DNA结合活性。在用各种抑制性化合物处理之前和之后，通过免疫荧光染色在每个CTCL细胞系中测量p65（Rel A）的核表达。24例MF中有22例肿瘤性T淋巴细胞显示活性p65（Rel A）在细胞核和细胞质中的强表达。与未处理的对照细胞相比，在化学NF-κ B抑制后，两种CTCL细胞系的细胞凋亡显著增加，NF-κ B DNA结合活性显著降低，核p65（Rel A）表达显著降低。这些数据表明NF-κ B p65（Rel A）的活性形式通常在MF患者的肿瘤性T淋巴细胞中表达。在CTCL细胞系中，核NF-κ B表达的显著降低和由化学NF-κ B抑制引起的自发性凋亡的显著增加表明NF-κ B在CTCL的发病机制和肿瘤细胞维持中起关键作用。《人文哲学》31：1482-1490。
The NF-kappa B family of transcription factors is an important regulator of genes expressed during inflammatory responses, immunoglobulin (Ig) class switching, cellular differentiation, and apoptosis. Recently, members of the NF-kappaB family, including p65(Rel A), have been implicated in promoting survival of various hematopoeitic neoplasms, including T cell malignancies such as adult T cell leukemia-lymphoma. We investigated the expression of active NF-kappa B p65(Rel A) in cases of mycosis fungoides (MF) and the effect of chemical inhibitors of NF-kappa B on apoptosis in cutaneous T cell lymphoma (CTCL) cell lines. Paraffin-embedded tissues from 23 cutaneous lesions and a single lymph node biopsy from patients diagnosed with MF were evaluated for p65(Rel A) expression by using a monoclonal mouse antibody that detects the activated form of p65(Rel A). Apoptosis after treatment with the NF-kappa B inhibitors gliotoxin, MG132, BAY 11-7082, and BAY 11-7085 was quantitatively measured in the CTCL cell lines HuT-78 and HH by propidium iodide (PI)/cell cycle analysis for detection of a hypodiploid (sub-G(0)) population and by determination of increased Annexin V/7-amino-actinomycin D (7-AAD) expression. Nuclear extracts from CTCL cells before and after chemical inhibition were analyzed for NF-kappa B nuclear DNA-binding activity by electrophoretic mobility shift assay (EMSA) with quantitative densitometry. Nuclear expression of p65(Rel A) before and after treatment with the various inhibitory compounds was measured by immunofluorescence staining in each CTCL cell line. Neoplastic T lymphocytes from 22 of 24 cases of MF showed strong nuclear and cytoplasmic expression of active p65(Rel A). Compared with untreated control cells, a marked increase in apoptosis, a significant decrease in NF-kappa B DNA-binding activity, and a marked decrease in nuclear p65(Rel A) expression were seen in cells from both CTCL cell lines after chemical NF-kappa B inhibition. These data show that the active form of NF-kappa B p65(Rel A) is commonly expressed in neoplastic T lymphocytes in patients with MF. In CTCL cell lines, the significant decrease in nuclear NF-kappa B expression and the marked increase in spontaneous apoptosis caused by chemical NF-kappa B inhibition suggest a critical role for NF-kappa B in the pathogenesis and tumor cell maintenance of CTCLs. HUM PATHOL 31:1482-1490.
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影响因子：
8
作者：
Jiandong Zhang;C. Chang;Luigia Lombardi;Riccardo Dalla-Favera
通讯作者：
Jiandong Zhang;C. Chang;Luigia Lombardi;Riccardo Dalla-Favera
v-Rel 癌蛋白可阻断转化鸡脾细胞中 I kappa B-alpha 的凋亡和蛋白水解。
影响因子：
8
作者：
White,DW;Roy,A;Gilmore,TD
通讯作者：
Gilmore,TD
影响因子：
20.3
作者：
R. Feinman;J. Koury;M. Thames;B. Barlogie;J. Epstein;D. Siegel
通讯作者：
R. Feinman;J. Koury;M. Thames;B. Barlogie;J. Epstein;D. Siegel
DOI：
10.1073/pnas.88.13.5857
发表时间：
1991-07-01
影响因子：
11.1
作者：
NEIMAN, PE;THOMAS, SJ;LORING, G
通讯作者：
LORING, G
影响因子：
1.8
作者：
Atta, Ananta Kumar;Ahn, In-Ho;Cho, Dong-Gyu
通讯作者：
Cho, Dong-Gyu