Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesis.
Role of 'platelet-type' 12-lipoxygenase in skin carcinogenesis.
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“血小板型”12-脂氧合酶在皮肤癌发生中的作用。
DOI：
10.1016/s0304-3835(00)00634-0
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发表时间：
2001
期刊：
影响因子：
9.7
通讯作者：
Funk,CD
中科院分区：
文献类型：
--
作者：
Virmani,J;Johnson,EN;Klein-Szanto,AJ;Funk,CD
小鼠和人类皮肤表达丰富的脂氧合酶同工型，其功能尚不清楚。大量数据表明，“血小板型”12-脂氧合酶（P-12 LO）代谢产物12（S）-羟基-二十碳四烯酸（12-HETE）在多种肿瘤功能中发挥作用。使用P-12 LO缺陷小鼠，我们试图研究P-12 LO途径在肿瘤发生和发展中的作用。两个不同的遗传株的P-12 LO缺陷和野生型小鼠，B6/129 Sv和SENCAR，在两个阶段的致癌实验进行了评估。在B6/129 Sv背景的P-12 LO缺陷小鼠中，癌症发病率显著降低，但在SENCAR回交小鼠中则没有。相比之下，SENCAR背景下的乳头状瘤发病率降低，但在B6/129 Sv品系小鼠中没有。一个单独的实验采用了一个完整的致癌协议未能发现任何差异乳头状瘤或癌的发病率。总体而言，这些数据表明，P-12 LO通路可能有助于肿瘤的发病率和进展，在两个阶段，但不完全，致癌，这取决于遗传背景。
Murine and human skin express an abundance of lipoxygenase isoforms whose functions are not understood. Substantial data have implicated a role for the ‘platelet-type’ 12-lipoxygenase (P-12LO) metabolite, 12(S)-hydroxy-eicosatetraenoic acid (12-HETE), in a variety of tumor functions. Using P-12LO deficient mice, we sought to examine the role of the P-12LO pathway in tumor initiation and progression. Two distinct genetic strains of P-12LO deficient and wild-type mice, B6/129 Sv and SENCAR, were evaluated in two-stage carcinogenesis experiments. Carcinoma incidence was significantly reduced in the P-12LO deficient mice of the B6/129 Sv background but not the SENCAR-backcrossed mice. In contrast, papilloma incidence was reduced on the SENCAR background but not in the B6/129 Sv strain mice. A separate experiment employing a complete carcinogenesis protocol failed to find any difference in papilloma or carcinoma incidence. Overall, these data suggest that the P-12LO pathway may contribute to tumor incidence and progression in two-stage, but not complete, carcinogenesis, depending on the genetic background.