MMTV-Fgf8 transgenic mice develop mammary and salivary gland neoplasia and ovarian stromal hyperplasia
MMTV-Fgf8 transgenic mice develop mammary and salivary gland neoplasia and ovarian stromal hyperplasia
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DOI：
10.1038/sj.onc.1202212
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发表时间：
1998-11-26
期刊：
影响因子：
8
通讯作者：
MacArthur, CA
中科院分区：
文献类型：
--
作者：
Daphna-Iken, D;Shankar, DB;MacArthur, CA
先前的研究已确定成纤维细胞生长因子 8 (Fgf8) 可能是小鼠乳腺肿瘤发生中的原癌基因。我们现在报告了两种类型的 Fgf8 转基因小鼠的产生，每种小鼠都利用小鼠乳腺肿瘤病毒 (MMTV) 启动子。第一个转基因 (MMTV-Fgf8b) 仅导致 FGF8b 同种型的过度表达。雄性和雌性 MMTV-Fgf8b 转基因小鼠均能存活且具有生育能力。通过 Northern 印迹分析，在转基因小鼠的乳腺和唾液腺组织中检测到 FGF8b RNA。近 85% 的转基因雌性小鼠在 12 个月大时会患上乳腺小叶腺癌，而非转基因同窝小鼠则不会患上乳腺小叶腺癌。唾液腺肿瘤发生在一些动物中，总是与乳腺肿瘤相关。几只 MMTV-Fgf8b 转基因小鼠在尸检时出现肺转移。第二个转基因 (MMTV-Fgf8) 使用整个 Fgf8 基因并可能编码所有 FGF8 亚型。除上述组织外，该转基因还在多种组织中表达 Fgf8，尤其是卵巢。 MMTV-Fgf8 的两位创始人在 5 个月和 8 个月大时患上乳腺导管腺癌，并且都表现出卵巢间质增生。表达这两种转基因的创始人都没有成功地喂养他们的幼崽。这些结果表明，乳腺和唾液腺中 FGF8b 以及可能的其他 FGF8 同工型的产生有助于肿瘤发生，并且卵巢表达导致基质增生。
Prior studies have identified Fibroblast Growth Factor-8 (Fgf8) as a possible proto-oncogene in mouse mammary tumorigenesis. We now report on the generation of two types of Fgf8 transgenic mice that each utilize the mouse mammary tumor virus (MMTV) promoter. The first transgene (MMTV-Fgf8b) results in the overexpression of the FGF8b isoform exclusively. Male and female MMTV-Fgf8b transgenic mice are viable and fertile. RNA for FGF8b is detected in mammary gland and salivary gland tissues of transgenic mice by Northern blot analysis. Nearly 85% of breeding transgenic female mice developed mammary lobular adenocarcinomas by 12 months of age, while no tumors developed in nontransgenic littermates. Salivary gland tumors occurred in some animals, always in association with mammary tumors. Several MMTV-Fgf8b transgenic mice had lung metastases at necropsy. The second transgene (MMTV-Fgf8) uses the entire Fgf8 gene and potentially encodes all FGF8 isoforms. Fgf8 is expressed by this transgene in several tissues in addition to those described above, notably the ovaries. The two MMTV-Fgf8 founders developed mammary ductal adenocarcinomas at five and eight months of age, and both displayed ovarian stromal hyperplasia. The founders expressing either transgene did not successfully nurse their pups. These results demonstrate that production of FGF8b, and possibly other FGF8 isoforms, in the mammary and salivary glands contributes to oncogenesis, and that ovarian expression results in stromal hyperplasia.