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Shift and longtime light induces endometrioid adenocarcinoma via activation of PKC-α/Akt pathway in female golden hamster: Involvement of altered Aanat and Bmal1 rhythm
Journal of Pineal Research ( IF 10.3 ) Pub Date : 2023-06-26 , DOI: 10.1111/jpi.12894
Megha Das 1 , Chandana Haldar 1 , Sanjeev Kumar Yadav 1
Affiliation  

Female night-workers get exposed to frequent light shifts, hence have altered circadian rhythm and are at high risk of endometrial cancer; the underlying mechanism however is still not clear. We, therefore examined the effect of long light exposure (16L:8D, LD1) and regular shift (8 h) in long nighttime (LD2) on endometrial changes of female golden hamsters. Morphometric analysis, scanning electron microscopy imaging, alcian blue staining, and cytological nuclear atypia of endometrial stromal cells confirmed the incidence of endometrial adenocarcinoma in LD2 exposed hamsters. But, less severe pathomorphological alterations were noted in uterus of LD1 exposed hamsters. Altered Aanat and Bmal1 mRNA, melatonin rhythm, downregulation of important marker gene of adenocarcinoma like Akt, 14-3-3, and PR protein expression and upregulation PKCα, pAkt-S473 and vascular epithelial growth factor (VEGF) were observed in LD2 exposed hamsters suggesting the endometrial adenocarcinoma. Further, our western blot analysis supported the immunohistochemical localization of PR, PKCα, and VEGF in uterine tissues along low progesterone. Overall, our data indicates that light shift and long light exposure potentially induced endometrioid adenocarcinoma via activation of PKC-α/Akt pathway in female hamsters. Therefore, duration of light is essential for female normal uterine function.

中文翻译:

转变和长时间光照通过激活雌性金仓鼠的 PKC-α/Akt 通路诱导子宫内膜样腺癌:Aanat 和 Bmal1 节律改变的参与

女性夜班工作者经常暴露在光线变化下,因此昼夜节律发生改变,患子宫内膜癌的风险很高;然而,其根本机制仍不清楚。因此,我们研究了长时间光照(16L:8D,LD1)和长夜间定期轮班(LD2)对雌性金仓鼠子宫内膜变化的影响。子宫内膜基质细胞的形态测定分析、扫描电子显微镜成像、阿尔新蓝染色和细胞学核异型性证实了LD2暴露仓鼠中子宫内膜腺癌的发生率。但是,在 LD1 暴露仓鼠的子宫中发现了不太严重的病理形态学改变。在 LD2暴露的仓鼠中观察到 Aanat 和 Bmal1 mRNA、褪黑激素节律的改变、Akt、14-3-3 等腺癌重要标志基因和 PR 蛋白表达的下调以及 PKCα、pAkt-S473 和血管上皮生长因子 (VEGF )上调提示子宫内膜腺癌。此外,我们的蛋白质印迹分析支持 PR、PKCα 和 VEGF 在子宫组织中沿低孕酮水平的免疫组织化学定位。总体而言,我们的数据表明,光移和长时间光照可能通过激活雌性仓鼠中的 PKC-α/Akt 通路诱导子宫内膜样腺癌。因此,光照时间对于女性正常子宫功能至关重要。
更新日期:2023-06-26
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