FGF-8, ACTIVATED BY PROVIRAL INSERTION, COOPERATES WITH THE WNT-1 TRANSGENE IN MURINE MAMMARY TUMORIGENESIS
FGF-8, ACTIVATED BY PROVIRAL INSERTION, COOPERATES WITH THE WNT-1 TRANSGENE IN MURINE MAMMARY TUMORIGENESIS
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DOI：
10.1128/jvi.69.4.2501-2507.1995
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发表时间：
1995-04-01
影响因子：
5.4
通讯作者：
SHACKLEFORD, GM
中科院分区：
文献类型：
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作者：
MACARTHUR, CA;SHANKAR, DB;SHACKLEFORD, GM
我们用小鼠乳腺肿瘤病毒（MMTV）感染Wnt-1转基因小鼠，以加速乳腺肿瘤的发生，并对与Wnt-1（G. M.沙克尔福德角A.麦克阿瑟，H。C. Kwan和H. E. Varmus，Proc. Natl. Acad. Sci，USA 90：740-744，1993）。在这里，我们报告了一个31-kb的基因组位点，包含克隆MMTV整合在80个乳腺肿瘤的MMTV感染的Wnt-1转基因小鼠的识别和表征。两个基因被确定在这个位点，其中之一是转录激活MMTV插入。该激活的基因与雄激素诱导的生长因子（AIGF/Fgf-8）相同（A.田中角Miyamoto，N. Minamino，M.武田，B。佐藤，H。Matsuo和K.松本，Proc. Natl. Acad. Sci. USA 89：8928-8932，1992），成纤维细胞生长因子（FGF）家族的第八个成员。Fgf-8的转录激活被发现在MMTV插入在该位点的所有肿瘤中。FGF-8 mRNA在正常乳腺中不存在，仅在成年睾丸和卵巢以及妊娠中期胚胎中检测到。Fgf-8基因组和cDNA克隆的序列揭示了5个编码外显子，与在其他FGF基因中发现的3个编码外显子相反，分离出编码FGF-8蛋白的3种异构体的cDNA。这三个相应的mRNA分别来自第二和第三外显子的两个5'剪接位点和两个3'剪接位点的交替使用。这些结果暗示Fgf-8作为第三个发现与Wnt-1在MMTV诱导的小鼠乳腺肿瘤发生中合作的FGF基因，表明FGF和Wnt在此过程中是强有力的合作者。
We have used mouse mammary tumor virus (MMTV) infection of Wnt-1 transgenic mice to accelerate mammary tumorigenesis and to molecularly tag insertionally activated proto-oncogenes that Cooperate oncogenically with Wnt-1 (G. M. Shackleford, C. A. MacArthur, H. C. Kwan, and H. E. Varmus, Proc. Natl. Acad. Sci, USA 90:740-744, 1993). Here we report the identification and characterization of a 31-kb genomic locus that contains clonal MMTV integrations in 8 of 80 mammary tumors from MMTV-infected Wnt-1 transgenic mice. Two genes were identified within this locus, one of which was transcriptionally activated by MMTV insertions. This activated gene is identical to androgen-induced growth factor (AIGF/Fgf-8) (A. Tanaka, K. Miyamoto, N. Minamino, M. Takeda, B. Sato, H. Matsuo, and K. Matsumoto, Proc. Natl. Acad. Sci. USA 89:8928-8932, 1992), the eighth member of the fibroblast growth factor (FGF) family. Transcriptional activation of Fgf-8 was found in all tumors with MMTV insertions in this locus. Fgf-8 mRNA was absent in normal mammary glands and was detected only in adult testis and ovary and in midgestational embryos. The sequences of Fgf-8 genomic and cDNA clones revealed five coding exons, in contrast to the three coding exons found in other FGF genes, cDNAs encoding three isoforms of the FGF-8 protein were isolated. The three corresponding mRNAs resulted from the alternative use of two 5' splice sites and two 3' splice sites for the second and third exons, respectively. These results implicate Fgf-8 as the third FGF gene found to cooperate with Wnt-1 in MMTV-induced murine mammary tumorigenesis, suggesting that FGFs and Wnts are strong collaborators in this process.