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首页> 外文期刊>Cell and Tissue Research >PAD2 overexpression in transgenic mice augments malignancy and tumor-associated inflammation in chemically initiated skin tumors
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PAD2 overexpression in transgenic mice augments malignancy and tumor-associated inflammation in chemically initiated skin tumors

机译：转基因小鼠中的乳头2过表达增强了化学发起的皮肤肿瘤中的恶性肿瘤和肿瘤相关的炎症

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We previously found that transgenic mice overexpressing MMTV-FLAG-hPAD2 (PAD2OE) developed spontaneous skin lesions, with a subset of these lesions progressing to invasive squamous cell carcinoma (SCC). The goal of this report was to better understand the potential mechanisms by which PAD2 overexpression promotes skin cancer. Here, PAD2OE mice were treated with the carcinogen, 9,10-dimethyl-1,2-benzanthracene and with O-tetradecanoylphorbol-13-acetate and then scored for papilloma formation. Additionally, tumor sections were evaluated for evidence of tumor cell invasion and inflammation. We found that the total number of papillomas was significantly increased in PAD2OE mice compared to controls. Histopathologic analysis of the lesions found that in PAD2OE skin tumors progressed to invasive SCC more frequently than controls. Additionally, we found that PAD2OE lesions were highly inflamed, with a dense inflammatory cell infiltrate and an associated increase in nuclear phospho-STAT3 (signal transducer and activator of transcription 3) in the transgenic tumors. These data suggest that overexpression of the hPAD2 transgene in the epidermis increases the malignant conversion rate of benign tumors by promoting an inflammatory microenvironment.
机译：我们之前发现，过度表达MMTV-FLAG-hPAD2（PAD2OE）的转基因小鼠出现自发性皮肤病变，其中一部分病变进展为侵袭性鳞状细胞癌（SCC）。本报告的目的是更好地了解PAD2过度表达促进皮肤癌的潜在机制。在这里，用致癌物9,10-二甲基-1,2-苯并蒽和O-十四烷基佛波-13-醋酸盐治疗PAD2OE小鼠，然后对乳头状瘤的形成进行评分。此外，对肿瘤切片进行评估，以确定肿瘤细胞浸润和炎症的证据。我们发现，与对照组相比，PAD2OE小鼠的乳头状瘤总数显著增加。对病变的组织病理学分析发现，与对照组相比，PAD2OE皮肤肿瘤进展为侵袭性鳞状细胞癌的频率更高。此外，我们发现PAD2OE病变高度炎症，在转基因肿瘤中有密集的炎性细胞浸润和相关的核磷酸化STAT3（信号转导和转录激活因子3）增加。这些数据表明，表皮中hPAD2转基因的过度表达通过促进炎症微环境而增加良性肿瘤的恶性转化率。

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