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黄曲霉毒素 A 在小鼠皮肤中的增殖和致瘤作用及细胞周期蛋白 D1 和环氧化酶-2 表达的评估。

Cell Proliferation and Tumor Induction by Ochratoxin A in Mouse Skin and Evaluation of Cyclin D1 and Cyclooxygenase-2 Expressions.

机构信息

Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangdong Provincial Dermatology Hospital, China.

Department of Oncology, Guangzhou First People's Hospital, China.

出版信息

Comput Math Methods Med. 2021 Oct 25;2021:1723486. doi: 10.1155/2021/1723486. eCollection 2021.

DOI:10.1155/2021/1723486
PMID:34733352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8560303/
Abstract

. Skin tumor is one of the frequent occurring forms of cancer where 2-3 million instances are reported worldwide. The ultraviolet rays along with the environmental pollutants and other contaminants can be the potential factors of skin cancer. Cyclin D1 is a serious gene included in controlling the development through the G1 phase of the cell cycle. Ochratoxin A (OTA) is a naturally existing mycotoxin which majorly occurs in food like grains. It is responsible for producing the splitting of single-strand DNA and is identified to be cancer-causing. It is established as a critical risk factor towards reproductive health in both males and females. . A single dose of ochratoxin A was used for topical application for assessment of skin tumor promotion activity, hyperplasia, ornithine decarboxylase activity, and expression of cyclin D1 and COX-2 in mouse skin. Enhancement in the synthesis of DNA, activation of the epidermal growth factor receptor, and overexpression of cyclin D1 and COX-2 were noted. Primary murine keratinocyte cell culture was cultured with Waymouth's medium. Western blot analysis and real-time polymerase chain reaction (RT-PCR) were used to detect the expression of cyclin D1 and COX-2. Chromatin immunoprecipitation (ChIP) assays were used to the association between AP-1 transcription and nuclear factor-kappaB (NF-B) with COX-2 and cyclin D1 promoters. . The results found that cyclin D1 and COX-2 were responsible for stimulating OTA-induced PMK proliferation and hyperplasia. . EGFR-mediated pathways were also responsible for tumor promotion due to OTA.

摘要

皮肤肿瘤是癌症的常见形式之一,全世界报告的病例有 200 至 300 万例。紫外线以及环境污染物和其他污染物可能是皮肤癌的潜在因素。细胞周期蛋白 D1 是一种严重的基因,包含在通过细胞周期 G1 期的发育控制中。赭曲霉毒素 A(OTA)是一种天然存在的真菌毒素,主要存在于谷物等食物中。它负责产生单链 DNA 的断裂,被认为是致癌的。它被确定为男性和女性生殖健康的一个关键危险因素。

用单剂量的赭曲霉毒素 A 进行局部应用,以评估皮肤肿瘤促进活性、增生、鸟氨酸脱羧酶活性以及小鼠皮肤中环细胞蛋白 D1 和 COX-2 的表达。注意到 DNA 的合成增强、表皮生长因子受体的激活以及 cyclin D1 和 COX-2 的过表达。原代鼠角质形成细胞培养用 Waymouth 培养基培养。使用 Western blot 分析和实时聚合酶链反应(RT-PCR)检测 cyclin D1 和 COX-2 的表达。染色质免疫沉淀(ChIP)试验用于检测 AP-1 转录因子和核因子-kappaB(NF-B)与 COX-2 和 cyclin D1 启动子之间的关联。

结果发现,cyclin D1 和 COX-2 负责刺激 OTA 诱导的 PMK 增殖和增生。由于 OTA,EGFR 介导的途径也负责肿瘤促进。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/a367fdb8057f/CMMM2021-1723486.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/43e6f5a80ea0/CMMM2021-1723486.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/a9d7da8a8675/CMMM2021-1723486.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/0e3b3a1c8119/CMMM2021-1723486.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/6e25a3049dfe/CMMM2021-1723486.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/ba63c6dcf496/CMMM2021-1723486.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/a367fdb8057f/CMMM2021-1723486.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/43e6f5a80ea0/CMMM2021-1723486.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/5716a8f816a0/CMMM2021-1723486.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/0564158f0bee/CMMM2021-1723486.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/fabfb172aa2e/CMMM2021-1723486.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/a9d7da8a8675/CMMM2021-1723486.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/0e3b3a1c8119/CMMM2021-1723486.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/6e25a3049dfe/CMMM2021-1723486.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/ba63c6dcf496/CMMM2021-1723486.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8d3/8560303/a367fdb8057f/CMMM2021-1723486.009.jpg

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