Effects of COX-1 or COX-2 Deficiency on Mouse Skin Cancer

我们先前已经证明，在小鼠皮肤肿瘤发展过程中，β-抑制蛋白1和2与各种前列腺素受体形成复合物（Chun等人，Carcinogenesis，9：1620，2009）。因此，本研究的目的是阐明β-arrestin1或2缺乏对小鼠皮肤肿瘤的发展，使用多阶段小鼠皮肤肿瘤模型的影响。令人惊讶的是，β-arrestin 1减少了使用该模型的皮肤肿瘤的数量和大小;而β-arrestin 2的缺乏不影响肿瘤的数量，但实际上显着增加了肿瘤的大小。此外，虽然β-arrestin1缺乏减少p-ERK 1/2和考克斯-2的诱导，β-arrestin2缺乏增加p-ERK 1/2，但对考克斯-2的表达没有影响。进一步的研究正在进行中，以更好地阐明β-arrestin1和2缺乏对信号通路的影响，我们以前已经证明参与小鼠皮肤肿瘤的发展。 在卵巢癌的研究中，我们的结果表明，考克斯-1，但不是考克斯-2，缺乏减少小鼠卵巢癌的发展约50%。

We have previously demonstrated that beta-arrestin1 and 2 form complexes with various prostaglandin receptors during mouse skin tumor development (Chun et al., Carcinogenesis, 9:1620, 2009). Therefore, the goals of the present study were to elucidate the effects of beta-arrestin1 or 2 deficiency on mouse skin tumor development using the multi-stage mouse skin tumor model. Surprisingly, beta-arrestin 1 decreased the number and size of skin tumors using this model; whereas the deficiency of beta-arrestin2 did not effect the number of tumors but in fact significantly increased tumor size. Furthermore, while beta-arrestin1 deficiency decreased p-ERK1/2 and COX-2 induction, beta-arrestin2 deficiency increased p-ERK1/2 but had no effect on COX-2 expression. Further studies are underway to better elucidate the effects of beta-arrestin1 and 2 deficiency on the signaling pathways we have previously demonstrated to be involved in mouse skin tumor development. In the ovarian cancer studies, our results to date indicate that COX-1, but not COX-2, deficiency reduces mouse ovarian cancer development by about 50%.