PTEN 对类癌细胞系 BON 中 5-羟色胺合成和分泌的影响。
The effect of PTEN on serotonin synthesis and secretion from the carcinoid cell line BON.
机构信息
Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, USA.
出版信息
Anticancer Res. 2011 Apr;31(4):1153-60.
Abstract
BACKGROUND
Carcinoid tumors are associated with the carcinoid syndrome, a set of symptoms resulting from the peptide and amine products, including serotonin, secreted from the cancer cells. The purpose of this study was to investigate the relationship between the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) inhibitor PTEN (phosphatase and tensin homolog deleted on chromosome ten) and serotonin synthesis and secretion in the carcinoid cancer cell line BON.
MATERIALS AND METHODS
PTEN was inhibited by pharmacological and molecular approaches, and the resultant secretion of serotonin and expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin synthesis, was assessed.
RESULTS
Inhibition of PTEN in vitro, with concomitant increased Akt signaling, resulted in decreased secretion of serotonin, as well as decreased serotonin synthesis, as confirmed by reduced expression of TPH1. Inhibition of PTEN in BON cells in an animal model resulted in decreased serum serotonin.
CONCLUSION
By inhibiting signaling through Akt, PTEN indirectly promotes serotonin synthesis and secretion.
摘要
背景
类癌肿瘤与类癌综合征相关，这是一组由癌细胞分泌的肽和胺类产物（包括血清素）引起的症状。本研究的目的是研究磷脂酰肌醇-3-激酶/蛋白激酶 B（PI3K/Akt）抑制剂 PTEN（第十号染色体缺失的磷酸酶和张力蛋白同源物）与类癌细胞系 BON 中血清素合成和分泌之间的关系。
材料和方法
通过药理学和分子方法抑制 PTEN，并评估随之而来的血清素分泌和色氨酸羟化酶 1（TPH1）的表达，TPH1 是血清素合成的限速酶。
结果
体外抑制 PTEN，同时增加 Akt 信号，导致血清素分泌减少，以及血清素合成减少，这通过 TPH1 表达减少得到证实。在动物模型中抑制 BON 细胞中的 PTEN 导致血清素减少。
结论
通过抑制 Akt 信号转导，PTEN 间接促进血清素的合成和分泌。
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