Drakos Elias, Leventaki Vasiliki, Schlette Ellen J, Jones Dan, Lin Pei, Medeiros L Jeffrey, Rassidakis George Z
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Am J Surg Pathol. 2007 Mar;31(3):447-53. doi: 10.1097/01.pas.0000213412.25935.e4.
Cellular Jun (c-Jun), a member of the JUN family, is an activator protein-1 transcription factor involved in cell differentiation, proliferation, and apoptosis that can be activated by phosphorylation at serine-73 and -63 residues. Using tissue microarrays and immunohistochemistry, we investigated c-Jun expression and serine-73 phosphorylation in 112 CD30 lymphomas and 232 CD30 lymphomas of B- or T-cell lineage, and 24 cases of lymphomatoid papulosis. c-Jun was expressed exclusively by CD30 lymphoproliferative disorders including 41/41 (100%) classical Hodgkin lymphoma (cHL), 20/23 (87%) anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL), 18/26 (69%) ALK- ALCL, 5/9 (56%) primary cutaneous ALCL, 4/11 (36%) CD30 diffuse large B-cell lymphoma (DLBCL), and 11/24 (46%) cases of lymphomatoid papulosis. The percentage of c-Jun-positive tumor cells was highest in cHL and ALCL (P=0.002). In contrast, all CD30 lymphomas, including nodular lymphocyte predominant HL and CD30 non-Hodgkin lymphomas of B- or T-cell lineage were negative for c-Jun. Serine-73 phosphorylated c-Jun (p-c-Jun), the activated form of c-Jun, was expressed more frequently and at a higher level in cHL and ALK+ ALCL than other CD30 tumors. The percentage of p-c-Jun-positive tumor cells correlated significantly with the percentage of total c-Jun-positive cells (P<0.0001), suggesting that activated c-Jun positively regulates total c-Jun levels in CD30 lymphomas through a well-established positive feedback loop. We conclude that CD30 lymphomas are characterized by common patterns of c-Jun expression and activation suggesting a potential role of c-Jun in the pathogenesis of these tumors.
细胞 Jun（c-Jun）是 JUN 家族的成员，是一种激活蛋白-1 转录因子，参与细胞分化、增殖和凋亡，可通过丝氨酸-73 和-63 残基的磷酸化被激活。我们使用组织微阵列和免疫组织化学方法，研究了 112 例 CD30 淋巴瘤、232 例 B 或 T 细胞谱系的 CD30 淋巴瘤以及 24 例淋巴瘤样丘疹病中 c-Jun 的表达和丝氨酸-73 磷酸化情况。c-Jun 仅在 CD30 淋巴增殖性疾病中表达，包括 41/41（100%）的经典霍奇金淋巴瘤（cHL）、20/23（87%）的间变性淋巴瘤激酶（ALK）阳性间变性大细胞淋巴瘤（ALCL）、18/26（69%）的 ALK 阴性 ALCL、5/9（56%）的原发性皮肤 ALCL、4/11（36%）的 CD30 弥漫性大 B 细胞淋巴瘤（DLBCL）以及 11/24（46%）的淋巴瘤样丘疹病病例。c-Jun 阳性肿瘤细胞的百分比在 cHL 和 ALCL 中最高（P = 0.002）。相比之下，所有 CD30 淋巴瘤，包括结节性淋巴细胞为主型 HL 以及 B 或 T 细胞谱系的 CD30 非霍奇金淋巴瘤，c-Jun 均为阴性。丝氨酸-73 磷酸化的 c-Jun（p-c-Jun），即 c-Jun 的激活形式，在 cHL 和 ALK 阳性 ALCL 中比其他 CD30 肿瘤更频繁且更高水平地表达。p-c-Jun 阳性肿瘤细胞的百分比与总 c-Jun 阳性细胞的百分比显著相关（P < 0.0001），表明激活的 c-Jun 通过一个成熟的正反馈环正向调节 CD30 淋巴瘤中总 c-Jun 的水平。我们得出结论，CD30 淋巴瘤的特征在于 c-Jun 表达和激活的共同模式，提示 c-Jun 在这些肿瘤的发病机制中可能发挥作用。
