Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Clin Exp Dermatol. 2013 Dec;38(8):890-6. doi: 10.1111/ced.12102.
The c-Jun N-terminal kinase (JNK) is thought to be involved in inflammation, proliferation and apoptosis.
To examine the role of JNK isoforms in metastasis, proliferation, migration and invasion of the malignant melanoma (MM) cell lines SK-MEL-28, SK-MEL-3 and WM164, using a kinase-specific inhibitor or isoform-specific small interfering (si)RNAs.
SK-MEL-3, a cell line established from metastatic MM, showed slightly increased phosphorylation of both JNK1 and JNK2, whereas WM164, a cell line derived from primary MM, showed significant phosphorylation of JNK1. A JNK inhibitor, SP600125, inhibited cell proliferation of SK-MEL-3 but not SK-MEL-28 or WM164. Transfection of JNK1-specific siRNA reduced the migratory activity of WM164 cells, while silencing of either JNK1 or JNK2 strongly suppressed the invasive activity of SK-MEL-3.
Our study suggests that JNK isoforms have different roles in MM. Metastasis of MM may be regulated by JNK2, while invasion is regulated by both JNK1 and JNK2. JNK1 and JNK2 respectively mediate cell migration and cell proliferation. Further understanding of the specific roles of JNK isoforms in the pathogenesis of MM may lead to the development of therapies targeting specific isoforms.
c-Jun N-末端激酶（JNK）被认为参与炎症、增殖和细胞凋亡。
使用激酶特异性抑制剂或同工型特异性小干扰（si）RNA，研究 JNK 同工型在恶性黑色素瘤（MM）细胞系 SK-MEL-28、SK-MEL-3 和 WM164 的转移、增殖、迁移和侵袭中的作用。
从转移性 MM 建立的细胞系 SK-MEL-3 中 JNK1 和 JNK2 的磷酸化略有增加，而从原发性 MM 衍生的细胞系 WM164 中 JNK1 则显著磷酸化。JNK 抑制剂 SP600125 抑制 SK-MEL-3 的细胞增殖，但不抑制 SK-MEL-28 或 WM164。JNK1 特异性 siRNA 的转染降低了 WM164 细胞的迁移活性，而 JNK1 或 JNK2 的沉默强烈抑制了 SK-MEL-3 的侵袭活性。
我们的研究表明，JNK 同工型在 MM 中具有不同的作用。MM 的转移可能受 JNK2 调节，而侵袭则受 JNK1 和 JNK2 共同调节。JNK1 和 JNK2 分别介导细胞迁移和细胞增殖。进一步了解 JNK 同工型在 MM 发病机制中的特定作用可能导致针对特定同工型的治疗方法的发展。
