Maspin expression inversely correlates with breast tumor progression in MMTV/TGF-alpha transgenic mouse model.
Maspin expression inversely correlates with breast tumor progression in MMTV/TGF-alpha transgenic mouse model.
复制标题
在 MMTV/TGF-α 转基因小鼠模型中，Maspin 表达与乳腺肿瘤进展呈负相关。
作者：
Reddy,KB;McGowen,R;Schuger,L;Visscher,D;Sheng,S
Maspin是一种新型丝氨酸蛋白酶抑制剂，具有肿瘤抑制活性。迄今为止，尽管越来越多的证据表明maspin在乳腺癌和前列腺癌中的潜在诊断/预后和治疗价值，但缺乏合适的动物模型阻碍了对maspin在肿瘤进展的不同阶段的作用的体内研究。本研究利用MMTV/TGF-α转基因小鼠模型，研究maspin在乳腺肿瘤发生发展过程中的表达谱。MMTV/TGF-α转基因小鼠的组织学检查显示TGF-α表达导致乳腺过度增殖、增生和偶见癌。有趣的是，当MMTV/TGF-α转基因小鼠被繁殖为纯合子时，它们也发生了特征性的皮肤乳头状瘤。TGF-α转基因小鼠乳腺组织中maspin表达的免疫组织化学分析显示，maspin表达下调与肿瘤进展直接相关。maspin表达的缺失伴随着原位癌向浸润癌的关键转变。随后的原位杂交分析表明，下调maspin表达主要是一个转录事件。该数据与maspin的肿瘤抑制作用一致。MMTV/TGF-α转基因小鼠模型有利于在体内研究乳腺癌多阶段缓慢癌变过程中maspin的表达及其生物学功能。
Maspin is a novel serine protease inhibitor (serpin) with tumor suppressive activity. To date, despite the mounting evidence implicating the potential diagnostic/prognostic and therapeutic value of maspin in breast and prostate carcinoma, the lack of a suitable animal model hampers the in vivo investigation on the role of maspin at different stages of tumor progression. In this study, we used MMTV/TGF-α transgenic mouse model to study the expression profile of maspin in mammary tumor progression. Histopathological examinations of MMTV/TGF-α transgenic mice revealed TGF-α expression leading to hyperproliferation, hyperplasia, and occasional carcinoma in mammary gland. Interestingly, when MMTV/TGF-α transgenic mice were breed to homozygocity, they also developed characteristic skin papillomas. Immunohistochemistry analysis of maspin expression in the breast tissues of TGF-α transgenic mice showed a direct correlation between down-regulation of maspin expression and tumor progression. The loss of maspin expression was concomitant with the critical transition from carcinoma in situ to invasive carcinoma. Subsequent in-situ hybridization analyses suggest that the down-regulation of maspin expression is primarily a transcriptional event. This data is consistent with the tumor suppressive role of maspin. Furthermore, our data suggests that MMTV/TGF-α transgenic mouse model is advantageous for in vivo evaluation of both the expression and the biological function of maspin during the slow multi-stage carcinogenesis of mammary gland.