c-Jun promotes whereas JunB inhibits epidermal neoplasia.
c-Jun promotes whereas JunB inhibits epidermal neoplasia.
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DOI：
10.1038/jid.2011.1
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发表时间：
2011-05
影响因子：
6.5
通讯作者：
Zhang, Jennifer Y.
中科院分区：
文献类型：
--
作者：
Jin, Jane Y.;Ke, Hengning;Hall, Russell P.;Zhang, Jennifer Y.
AP1家族基因调节因子的去调控与包括癌症在内的多种疾病有关。在此，我们报道在人鳞状细胞癌（SCC）中c - Jun被激活，并且在再生人皮肤移植模型中，c - Jun与致癌Ras共表达足以将原代人表皮细胞转化为恶性细胞。相比之下，在大多数人SCC细胞中JunB未被诱导。此外，JunB的外源表达抑制了由Ras驱动的肿瘤发生或自发性人SCC细胞的肿瘤发生。相反，显性负性JunB突变体（DNJunB）促进肿瘤发生，这与相应的c - Jun突变体的肿瘤抑制功能相反。在细胞水平上，JunB以细胞自主的方式诱导表皮细胞衰老并减缓细胞生长。一致地，JunB和Ras共表达诱导表皮过早分化，同时p16和丝聚蛋白上调，细胞周期蛋白D1和CDK4下调。这些发现表明JunB和c - Jun对细胞生长和分化的调节不同，并对表皮肿瘤形成产生相反的影响。
Deregulation of the AP1 family gene regulators have been implicated in a wide range of diseases, including cancer. Here, we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclinD1 and CDK4. These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.
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影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
Schorpp-Kistner, M
影响因子：
8
作者：
Dhar, A;Hu, J;Colburn, NH
通讯作者：
Colburn, NH
影响因子：
64.5
作者：
CHIU, R;ANGEL, P;KARIN, M
通讯作者：
KARIN, M
DOI：
10.1083/jcb.132.6.1115
发表时间：
1996-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fialka I;Schwarz H;Reichmann E;Oft M;Busslinger M;Beug H
通讯作者：
Beug H
影响因子：
3.7
作者：
BRIATA, P;DANNA, F;GHERZI, R
通讯作者：
GHERZI, R