Hariri Mehrdad, Wood Geoffrey A, DiGrappa Marco A, MacPherson Michelle, Backman Stephanie A, Yaffe Martin J, Mak Tak W, Boyd Norman F, Khokha Rama
Department of Medical Biophysics, Ontario Cancer Institute/University Health Network, Toronto, Ontario, Canada.
Breast Cancer Res. 2004;6(5):R540-5. doi: 10.1186/bcr901. Epub 2004 Jul 9.
Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density.
We performed individual manipulations of the stromal, epithelial and matrix components of the mouse mammary gland and examined the alterations using in vivo and ex vivo radiology, whole mount staining and histology.
Areas of density were generated that resembled densities in mammographic images of the human breast, and the nature of the imposed changes was confirmed at the cellular level. Furthermore, two genetic models, one deficient in epithelial structure (Pten conditional tissue specific knockout) and one with hyperplastic epithelium and mammary tumors (MMTV-PyMT), were used to examine radiographic density.
Our data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse.
女性乳腺钼靶密度增高与乳腺癌风险增加相关。小鼠模型为人类疾病研究提供了一种强大的方法，但目前尚无适合研究乳腺钼靶密度的模型。
我们对小鼠乳腺的基质、上皮和基质成分进行了单独操作，并使用体内和体外放射学、整体染色和组织学检查了这些改变。
产生了类似于人类乳腺钼靶图像中密度的区域，并且在细胞水平上证实了所施加变化的性质。此外，使用了两种遗传模型，一种上皮结构缺陷（Pten条件性组织特异性敲除），另一种具有增生性上皮和乳腺肿瘤（MMTV-PyMT），来检查放射密度。
我们的数据表明，通过实验和遗传手段改变和成像小鼠乳腺放射密度是可行的，这为模拟小鼠乳腺钼靶密度相关生物学过程迈出了第一步。
