β2-AR regulates the expression of AKR1B1 in human pancreatic cancer cells and promotes their proliferation via the ERK1/2 pathway
β2-AR regulates the expression of AKR1B1 in human pancreatic cancer cells and promotes their proliferation via the ERK1/2 pathway
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β2-AR 调节人胰腺癌细胞中 AKR1B1 的表达并通过 ERK1/2 途径促进其增殖
DOI：
10.1007/s11033-018-4332-3
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发表时间：
2018-12-01
影响因子：
2.8
通讯作者：
Chen, Wei-Chang
中科院分区：
文献类型：
--
作者：
Xiao, Ming-Bing;Jin, Dan-Dan;Chen, Wei-Chang
心理应激被认为是胰腺癌发生中与β 2-肾上腺素能受体（β 2-AR）相关的危险因素。Aldo-keto还原酶1成员B1 （AKR1B1）是β 2-AR的潜在相互作用伙伴，但其相互作用对胰腺癌细胞的影响目前尚不清楚。我们发现AKR1B1和β 2-AR在胰腺癌组织样本中的表达呈正相关，并且这些蛋白在人胰腺癌BXPC-3细胞系中共定位。与对照组相比，过表达β 2-AR和AKR1B1的CFPAC-1和PANC-1胰腺癌细胞的增殖率明显更高，这是由于S期细胞比例更高，早期凋亡细胞比例降低。此外，β 2-AR的过表达导致AKR1B1和磷酸化的细胞外信号调节激酶（p-ERK1/2）的表达显著增加。过表达AKR1B1显著降低β 2-AR水平，升高p-ERK1/2。综上所述，β 2-AR在胰腺癌细胞中直接与AKR1B1相互作用，上调AKR1B1，通过ERK1/2通路促进其增殖，抑制细胞凋亡。我们的研究结果还强调了β 2-AR-AKR1B1轴作为胰腺癌的潜在治疗靶点。
Psychological stress has been recognized as a well-documented risk factor associated with beta 2-adrenergic receptor (beta 2-AR) in the development of pancreatic cancer. Aldo-keto reductase 1 member B1 (AKR1B1) is a potential interacting partner of beta 2-AR, but the effect of their interaction on pancreatic cancer cells is not known at present. We found a positive correlation between AKR1B1 and beta 2-AR expression in pancreatic cancer tissue samples, and co-localization of these proteins in the human pancreatic cancer BXPC-3 cell line. Compared to the controls, the CFPAC-1 and PANC-1 pancreatic cancer cells overexpressing beta 2-AR and AKR1B1 respectively showed significantly higher proliferation rates, which is attributed to higher proportion of cells in the S phase and decreased percentage of early apoptotic cells. Furthermore, overexpression of beta 2-AR led to a significant increase in the expression of AKR1B1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Overexpression of AKR1B1 significantly decreased beta 2-AR levels and increased that of p-ERK1/2. Taken together, beta 2-AR directly interacted with and up-regulated AKR1B1 in pancreatic cancer cells, and promoted their proliferation and inhibited apoptosis via the ERK1/2 pathway. Our findings also highlight the beta 2-AR-AKR1B1 axis as a potential therapeutic target for pancreatic cancer.