15-lipoxygenase-1 expression upregulates and activates insulin-like growth factor-1 receptor in prostate cancer cells
15-lipoxygenase-1 expression upregulates and activates insulin-like growth factor-1 receptor in prostate cancer cells
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DOI：
10.1016/s1476-5586(04)80052-6
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Cohen, C
中科院分区：
文献类型：
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作者：
Kelavkar, UP;Cohen, C
我们以前发现，脂肪代谢酶，15-脂氧合酶-1（15-LO-1），在人类前列腺癌（PCa）中含量较高，并与疾病进展相关。PCa中异常的15-LO-1/亚油酸（LA）代谢与脂肪（生长因子的丰富来源）之间的生物学联系尚不清楚。因此，我们检验了多不饱和脂肪酸LA的代谢产物（即，13-S-羟基十八碳二烯酸或13-（S）-HODE）通过一种或多种生长因子影响PCa细胞的增殖状态。我们使用亲本前列腺癌细胞系-3（PC-3）和工程改造的PC-3细胞系[PC 3-Zeo（模拟转染）、PC 3 - 15 LOS（15-LO-1-过表达）和PC 3 - 15 LOAS（15-LO-1-阻断）]来检验我们的假设。在检测的生长因子中，只有胰岛素样生长因子-1（IGF-1）在PC 3 - 15 LOS细胞上的生长反应比PC 3-Zeo（对照）细胞系增加2 - 3倍（P
We previously discovered that a fat-metabolizing enzyme, 15-lipoxygenase-1 (15-LO-1), is high in human prostate cancer (PCa) and correlates with disease progression. The biologic link between the aberrant 15-LO-1/linoleic acid (LA) metabolism and fat (which is a rich source of growth factors) in PCa is unknown. Therefore, we tested the hypothesis that the metabolic product of the polyunsaturated fatty acid LA (i.e., 13-S-hydroxyoctadecadienoic acid or 13-(S)-HODE) affects the proliferation status of PCa cells through one or more growth factors. We used parental prostate cancer cell line-3 (PC-3) and engineered PC-3 cell lines [PC3-Zeo (mock-transfected), PC3-15LOS (15-LO-1-overexpressing), and PC3-15LOAS (15-LO-1-blocked)] to test our hypothesis. Of the growth factors examined, only insulin-like growth factor-1 (IGF-1) exhibited a two-fold to three-fold increase in growth response on PC3-15LOS cells compared to PC3-Zeo (control) cell line (P