Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth
Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth
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DOI：
10.1038/sj.onc.1205172
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发表时间：
2002-02-07
期刊：
影响因子：
8
通讯作者：
Van Horn, K
中科院分区：
文献类型：
--
作者：
Silberstein, GB;Dressler, GR;Van Horn, K
在这项研究中，我们首先描述了配对结构域转录因子PAX2在正常和癌组织中的表达，然后在小鼠模型中展示了PAX2在孕酮刺激的次级导管生长调节中的新功能。在人类乳腺组织中，PAX2的表达与乳腺导管细胞亚群一致，其中一些具有未分化的组织类型，在所调查的人类乳腺肿瘤中也发现了PAX2的表达(n=38)。在小鼠中，靶向缺失PAX2的乳腺实质在移植到野生型宿主乳房脂肪垫中时发育出正常的导管系统，但未能对黄体酮产生更高级别的侧枝和小叶发育。在乳腺中还发现了一个先前未被怀疑的PAX2/WT1(Wilms肿瘤抑制基因)调节轴。RT-PCR检测到突变的PAX2腺体中WT1mRNA的表达显著低于野生型，双抗体免疫组织化学检测到PAX2和WT1在正常和癌变乳腺细胞的细胞核中共存。这些数据表明，PAX2(可能还有WT1)在成熟乳腺孕酮反应的调节中起作用。讨论了PAX2在乳腺肿瘤发病机制中的潜在作用。
In this study, we first describe expression of the paired domain transcription factor PAX2 in the normal and cancerous human breast, then demonstrate in a murine model a novel function for PAX2 in the regulation of progesterone stimulation of secondary ductal growth. In human mammary tissue, PAX2 expression was coincident with sub-populations of mammary ductal cells, some of which possessed an undifferentiated histiotype, and was also found in >50% of the human breast tumors surveyed (n=38). In the mouse, mammary parenchyma with a targeted deletion of PAX2 developed normal ductal systems when grafted into wild-type host mammary fat pads, but failed to undergo higher order side-branching and lobular development in response to progesterone. A previously unsuspected PAX2/WT1 (Wilms' tumor suppressor gene) regulatory axis in the mammary gland was also indicated. Using RT-PCR, a significant reduction in WT1 mRNA expression was detected in the PAX2 mutant glands compared to wildtype counterparts and double-antibody immunohistochemistry detected the co-localization of PAX2 and WT1 in the nuclei of normal and cancerous breast cells. These data indicate a role for PAX2 (and possibly WT1) in the regulation of the progesterone response of the mature mammary gland. The potential contribution of PAX2 to breast tumor pathogenesis is discussed.