Lactotransferrin: A candidate tumor suppressor - Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen-activated protein kinase pathway
Lactotransferrin: A candidate tumor suppressor - Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen-activated protein kinase pathway
复制标题
DOI：
10.1002/ijc.23727
复制
发表时间：
2008-11-01
影响因子：
6.4
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
--
作者：
Zhou, Yanhong;Zeng, Zhaoyang;Li, Guiyuan
乳转铁蛋白（LTF）已被证明调节肿瘤的发生。然而，关于LTF在调节人鼻咽癌（NPC）发展中的作用知之甚少。我们的研究目的是通过cDNA和组织微阵列技术表征人鼻咽癌组织中LTF的表达模式，探讨LTF是否可以调节鼻咽癌的发展。与非肿瘤鼻咽上皮组织相比，鼻咽癌组织中LTF表达缺失的频率明显更高。T1/T2期鼻咽癌组织中有61.25%的组织表达LTF阳性，而T3/T4期鼻咽癌组织中只有40.82%的组织被抗LTF染色。LTF在局部淋巴结转移的鼻咽癌中表达率为41.58%，显著低于原发肿瘤的46.36% （p < 0.05）。这些结果表明，LTF可能在体内负向调节鼻咽癌的发展和转移。此外，LTF过表达或处理可抑制鼻咽癌细胞的增殖，并促进细胞周期在体外G(0)/G(1)期停滞。虽然LTF处理下调了细胞周期蛋白D1的表达和视网膜母细胞瘤蛋白（Rb）的磷酸化，但在5-8F鼻咽癌细胞中p21和p27的表达增强。此外，LTF处理可调节丝裂原活化蛋白激酶（MAPK）通路，但不影响5-8F鼻咽癌细胞中p53和STAT3的表达。因此，LTF可能是一种候选的肿瘤抑制因子，通过诱导细胞周期阻滞和调节MAPK信号通路抑制鼻咽癌的增殖，从而下调鼻咽癌的发展。因此，我们的研究结果为理解LTF在调节人类鼻咽癌发展中的作用机制提供了新的见解。(c) 2008 Wiley-Liss, Inc。
Lactotransferrin (LTF) has been shown to regulate tumorogenesis. However, little is known about the role of LTF in regulating the development of human nasopharyngeal carcinoma (NPC). The aim of our study was to investigate whether LTF could regulate the development of NPC by characterizing the pattern of LTF expression in human NPC tissues using cDNA and tissue microarrays. Loss of LTF expression was observed in a significantly higher frequency of NPC tissues compared to that in non-tumor nasopharyngeal epithelial tissues. While 61.25% of NPC tissues at the T1/T2 stage were positive for LTF expression, only 40.82% of NPC at the T3/T4 stage were stained by anti-LTF. Similarly, 41.58% of NPC with local lymph node metastasis displayed LTF expression, a value significantly lower than the 46.36% in primary tumors (p < 0.05). These findings suggest that LTF may negatively regulate the development and metastasis of NPC in vivo. Furthermore, overexpression of or treatment with LTF inhibited the proliferation of NPC cells and promoted cell cycle arrest at the G(0)/G(1) phase in vitro. While LTF treatment downregulated expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb), expression of p21 and p27 in 5-8F NPC cells was enhanced. Moreover, LTF treatment modulated the mitogen-activated protein kinase (MAPK) pathway, but did not affect p53 and STAT3 expression in 5-8F NPC cells. Thus LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway. Therefore, our findings provide new insights in understanding the mechanism(s) underlying the action of LTF in regulating the development of human NPC. (c) 2008 Wiley-Liss, Inc.