High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR.

High glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR.
复制标题

高血糖通过诱导 EGF 表达和 EGFR 反式激活促进胰腺癌细胞增殖

DOI:
10.1371/journal.pone.0027074
复制
发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Wu E
Wu E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Han L;Ma Q;Li J;Liu H;Li W;Ma G;Xu Q;Zhou S;Wu E

文献摘要

参考文献

被引文献

相似文献

多种证据表明,很大一部分胰腺癌患者要么患有高血糖,要么患有糖尿病,这两种疾病的特征都是高血糖水平。然而,这种现象的潜在生物学机制在很大程度上是未知的。在本研究中,我们证明了两种人胰腺癌细胞系BxPC-3和PANC-1的增殖能力在高糖作用下呈浓度依赖性地上调。此外,利用EGF中和抗体和RT-PCR检测了高糖对PC细胞EGF转录和分泌的促进作用,但对其受体的促进作用不明显。此外,在存在EGF中和抗体的情况下,高糖水平以浓度和时间依赖的方式在PC细胞中诱导EGFR反式激活。这些结果提示,高糖通过诱导EGF表达和反式激活EGFR促进胰腺癌细胞的增殖。我们的发现可能从分子机制上为高血糖与PC之间的联系提供新的见解,并为同时患有糖尿病或高血糖的PC患者提供一种新的治疗策略。
Multiple lines of evidence suggest that a large portion of pancreatic cancer patients suffer from either hyperglycemia or diabetes, both of which are characterized by high blood glucose level. However, the underlying biological mechanism of this phenomenon is largely unknown. In the present study, we demonstrated that the proliferative ability of two human pancreatic cancer cell lines, BxPC-3 and Panc-1, was upregulated by high glucose in a concentration-dependent manner. Furthermore, the promoting effect of high glucose levels on EGF transcription and secretion but not its receptors in these PC cell lines was detected by using an EGF-neutralizing antibody and RT-PCR. In addition, the EGFR transactivation is induced by high glucose levels in concentration- and time-dependent manners in PC cells in the presence of the EGF-neutralizing antibody. These results suggest that high glucose promotes pancreatic cancer cell proliferation via the induction of EGF expression and transactivation of EGFR. Our findings may provide new insight on the links between high glucose level and PC in terms of the molecular mechanism and reveal a novel therapeutic strategy for PC patients who simultaneously suffer from either diabetes or hyperglycemia.
DOI: 10.1371/journal.pone.0017385
发表时间: 2011-02-28
期刊: PloS one
影响因子: 3.7
作者:
Li J;Ma Q;Liu H;Guo K;Li F;Li W;Han L;Wang F;Wu E
通讯作者: Wu E
DOI: 10.1016/j.canlet.2009.08.022
发表时间: 2010-04-01
期刊: CANCER LETTERS
影响因子: 9.7
作者:
Lee, EunAh;Yi, Jae Youn;Son, Youngsook
通讯作者: Son, Youngsook
DOI: 10.1152/ajprenal.00159.2001
发表时间: 2002-04-01
影响因子: 4.2
作者:
Gekle, M;Freudinger, R;Silbernagl, S
通讯作者: Silbernagl, S
DOI: 10.1074/jbc.271.1.563
发表时间: 1996-01-05
影响因子: 4.8
作者:
Soltoff, SP;Cantley, LC
通讯作者: Cantley, LC
DOI: 10.1016/j.cell.2008.08.021
发表时间: 2008-09-05
期刊: CELL
影响因子: 64.5
作者:
Hsu, Peggy P.;Sabatini, David M.
通讯作者: Sabatini, David M.