Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas

作者: Vassiliki Theodorou , Mandy Boer , Britta Weigelt , Jos Jonkers , Martin van der Valk

DOI: 10.1038/SJ.ONC.1207816

关键词: InsertionMammary glandMolecular biologyMouse mammary tumor virusOncogeneTransplantationBiologyInsertional mutagenesisCancer researchOncogenicityCarcinogenesis

摘要: Mouse mammary tumor virus (MMTV) infection causes a high incidence of murine carcinomas by insertion its proviral DNA in the genome epithelial cells. Retroviral can activate flanking proto-oncogenes process called insertional mutagenesis. By sequencing adjacent to MMTV insertions tumors from BALB/c mice infected with C3H-MMTV, we have found common site Fgf10 locus. RT–PCR studies showed that is expressed only those harboring this locus, suggesting proto-oncogene. The oncogenicity was evaluated vivo subcutaneous transplantation retrovirally transduced HC11 cells into mice. Highly vascularized invasive developed indicating act as an oncogene. A survey primary human breast revealed strongly elevated mRNA levels approximately 10% tested, may also be involved subset cancers.

参考文章(43)
David Jackson, Janine Bresnick, Clive Dickson, A Role for Fibroblast Growth Factor Signaling in the Lobuloalveolar Development of the Mammary Gland Journal of Mammary Gland Biology and Neoplasia. ,vol. 2, pp. 385- 392 ,(1997) , 10.1023/A:1026351414004
Frits Michiels, Rob A. Van Der Kammen, Lennert Janssen, Garry Nolan, John G. Collard, Expression of Rho GTPases using retroviral vectors. Methods in Enzymology. ,vol. 325, pp. 295- 302 ,(2000) , 10.1016/S0076-6879(00)25451-7
Safia J. Qureshi, David J. Porteous, Anthony J. Brookes, Alu-based vectorettes and splinkerettes Genetic Analysis: Biomolecular Engineering. ,vol. 11, pp. 95- 101 ,(1994) , 10.1016/1050-3862(94)90046-9
Keisuke Sekine, Hideyo Ohuchi, Masanori Fujiwara, Masahiro Yamasaki, Tatsuya Yoshizawa, Takashi Sato, Naoko Yagishita, Daisuke Matsui, Yoshihiko Koga, Nobuyuki Itoh, Shigeaki Kato, Fgf10 is essential for limb and lung formation Nature Genetics. ,vol. 21, pp. 138- 141 ,(1999) , 10.1038/5096
M. Sluyser, Jo Hilgers, Mammary tumors in the mouse. Elsevier/North-Holland Biomedical Press , Sole distributors for the U.S.A. and Canada, Elsevier North-Holland. ,(1981)
K. G. Danielson, C. J. Oborn, E. M. Durban, J. S. Butel, D. Medina, Epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro Proceedings of the National Academy of Sciences of the United States of America. ,vol. 81, pp. 3756- 3760 ,(1984) , 10.1073/PNAS.81.12.3756
H. Min, D. M. Danilenko, S. A. Scully, B. Bolon, B. D. Ring, J. E. Tarpley, M. DeRose, W. S. Simonet, Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless Genes & Development. ,vol. 12, pp. 3156- 3161 ,(1998) , 10.1101/GAD.12.20.3156
Akira Tanaka, Tomoko Kamiakito, Norio Takayashiki, Shinji Sakurai, Ken Saito, Fibroblast growth factor 8 expression in breast carcinoma: associations with androgen receptor and prostate-specific antigen expressions. Virchows Archiv. ,vol. 441, pp. 380- 384 ,(2002) , 10.1007/S00428-002-0687-9
Takeshi Suzuki, Haifa Shen, Keiko Akagi, Herbert C Morse, James D Malley, Daniel Q Naiman, Nancy A Jenkins, Neal G Copeland, New genes involved in cancer identified by retroviral tagging Nature Genetics. ,vol. 32, pp. 166- 174 ,(2002) , 10.1038/NG949