黑色素瘤中异质核核糖核蛋白 k 的高表达。
Higher expression of the heterogeneous nuclear ribonucleoprotein k in melanoma.
机构信息
Department of Surgery, Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
出版信息
Ann Surg Oncol. 2010 Oct;17(10):2619-27. doi: 10.1245/s10434-010-1121-1. Epub 2010 May 25.
BACKGROUND
The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. Oncogenes c-Src, c-myc, and eIF4E are regulated by hnRNP K. We have shown an increased cytoplasmic hnRNP K in pancreatic cancer. In the present study, we investigated the altered expression of hnRNP K protein and its correlation with p-ERK in melanoma using human melanoma cell lines and tissue microarray.
MATERIALS AND METHODS
The protein levels of hnRNP K and p-ERK in 8 human melanoma cell lines and a melanoma progression tissue microarray containing 80 melanoma, 23 dysplastic nevi, and 14 benign nevi specimens were analyzed using Western blot and immunohistochemistry analysis. hnRNP K was knocked down by siRNA, and its effect on melanoma cells was assessed.
RESULTS
We showed a higher hnRNP K protein level in both melanoma cell lines and melanoma tissue specimens, which correlated with a higher c-myc expression. An increase in the cytoplasmic hnRNP K and eIF4E protein levels in melanoma cells is also seen. p-ERK level was also higher in dysplastic nevi and melanoma tissues, but did not correlate with hnRNP K protein level. We then demonstrated that knocking down of hnRNP K by siRNA inhibited melanoma cell growth and colony formation, as well as c-myc expression.
CONCLUSIONS
hnRNP K expression correlated with melanoma and may play a role in melanoma tumorigenesis.
背景
异质核核糖核蛋白（hnRNP）K 是一种重要的 RNA 和 DNA 结合蛋白，参与基因表达和信号转导。hnRNP K 在癌症中的作用相对研究较少。然而，一些细胞功能强烈表明 hnRNP K 参与了肿瘤的发生。癌基因 c-Src、c-myc 和 eIF4E 受 hnRNP K 调节。我们已经在胰腺癌中观察到细胞质 hnRNP K 增加。在本研究中，我们使用人黑色素瘤细胞系和组织微阵列研究了 hnRNP K 蛋白的改变表达及其与黑色素瘤中 p-ERK 的相关性。
材料和方法
使用 Western blot 和免疫组织化学分析，分析了 8 个人黑色素瘤细胞系和一个包含 80 个黑色素瘤、23 个发育不良痣和 14 个良性痣标本的黑色素瘤进展组织微阵列中 hnRNP K 和 p-ERK 的蛋白水平。通过 siRNA 敲低 hnRNP K，并评估其对黑色素瘤细胞的影响。
结果
我们显示黑色素瘤细胞系和黑色素瘤组织标本中 hnRNP K 蛋白水平较高，与 c-myc 表达较高相关。黑色素瘤细胞中细胞质 hnRNP K 和 eIF4E 蛋白水平也增加。发育不良痣和黑色素瘤组织中的 p-ERK 水平也较高，但与 hnRNP K 蛋白水平无关。然后我们证明通过 siRNA 敲低 hnRNP K 抑制了黑色素瘤细胞的生长和集落形成，以及 c-myc 表达。
结论
hnRNP K 的表达与黑色素瘤相关，可能在黑色素瘤肿瘤发生中发挥作用。
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