The ETS transcription factor MEF is a candidate tumor suppressor gene on the X chromosome.

作者: Yoichiro Isohama , Mary Ann Suico , Tsuyoshi Shuto , Ayako Uto , Yoshiyuki Seki

DOI:

关键词: BiologyCell cultureX chromosomeCandidate Tumor Suppressor GeneMolecular biologyTumor suppressor geneTransfectionA549 cellCD31ETS transcription factor family

摘要: Although X chromosome transfer experiments indicated that tumor suppressor genes are present on the chromosome, they have not been previously identified. In this report, we show ETS transcription factor MEF (ELF4), which is located Xq26.1, possesses suppressive capability. expression was up-regulated by 5-azacytidine in some cancer cell lines. overexpression induced morphological changes, such as conversion of normally loose cell-cell contacts to strong interactions similar those seen presence matrix metalloproteinase (MMP) inhibitor BB94. colony formation assay, A549 cells, but MEF-overexpressing formed colonies soft agar culture. Furthermore, cells s.c. injected nude mice did grow, whereas control did. The tumors were poorly differentiated, well differentiated. By immunostaining with CD31, a marker vascular endothelial found angiogenesis significantly suppressed from cells. addition, conditioned media cultures stimulated migration human umbilical vein had less an effect. gelatin zymography, Western blotting analysis, and immunohistochemistry, levels MMP-9 MMP-2 reduced tumors. Immunohistochemical analyses showed interleukin (IL)-8 mice. IL-8 mRNA vitro down-regulated compared promoter activities encoding IL-8, ETS-2 these activities. Therefore, propose candidate gene opposite ETS-2.

参考文章(40)
I Rodrigo, A Fabra, A Cano, M Quintanilla, A Vinyals, E Lozano, L López-Barcons, A Llorens, M Gonzalez-Garrigues, Down-regulation of E-cadherin in mouse skin carcinoma cells enhances a migratory and invasive phenotype linked to matrix metalloproteinase-9 gelatinase expression Laboratory Investigation. ,vol. 78, pp. 1131- 1142 ,(1998)
Martine Duterque-Coquillaud, Markku Kurkinen, Dominique Stéhelin, Jean Phillippe Basuyaux, Giovanna Butticè, Séverine Carrère, Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex. Oncogene. ,vol. 13, pp. 2297- 2306 ,(1996)
Hiroyasu Esumi, Nobuyuki Sakurazawa, Masahiko Onda, Noritake Tanaka, Instability of X chromosome methylation in aberrant crypt foci of the human colon. Cancer Research. ,vol. 60, pp. 3165- 3169 ,(2000)
Gabriele Bergers, Rolf Brekken, Gerald McMahon, Thiennu H. Vu, Takeshi Itoh, Kazuhiko Tamaki, Kazuhiko Tanzawa, Philip Thorpe, Shigeyoshi Itohara, Zena Werb, Douglas Hanahan, Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis Nature Cell Biology. ,vol. 2, pp. 737- 744 ,(2000) , 10.1038/35036374
Yoshitake Nishimune, Norio Nonomura, Masami Nozaki, Kentaro Yomogida, Nobufumi Kanno, Akihiko Okuyama, Tsuneharu Miki, Masahiro Nozawa, Prostate-specific transcription factor hPSE is translated only in normal prostate epithelial cells. Cancer Research. ,vol. 60, pp. 1348- 1352 ,(2000)
Barry M. Kacinski, Eva Sapi, Sofya Rodov, Maryann B. Flick, Ets-2 transdominant mutant abolishes anchorage-independent growth and macrophage colony-stimulating factor-stimulated invasion by BT20 breast carcinoma cells Cancer Research. ,vol. 58, pp. 1027- 1033 ,(1998)
Maria Trojanowska, Ets factors and regulation of the extracellular matrix Oncogene. ,vol. 19, pp. 6464- 6471 ,(2000) , 10.1038/SJ.ONC.1204043
Andrew D. Sharrocks, A.Louise Brown, Yan Ling, Paula R. Yates, The ETS-domain transcription factor family The International Journal of Biochemistry & Cell Biology. ,vol. 29, pp. 1371- 1387 ,(1997) , 10.1016/S1357-2725(97)00086-1
A. G. Knudson, H. W. Hethcote, B. W. Brown, Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 72, pp. 5116- 5120 ,(1975) , 10.1073/PNAS.72.12.5116
Yixing Jiang, William N Rom, Ting-An Yie, Chuan Xiang Chi, Kam-Meng Tchou-Wong, Induction of tumor suppression and glandular differentiation of A549 lung carcinoma cells by dominant-negative IGF-I receptor. Oncogene. ,vol. 18, pp. 6071- 6077 ,(1999) , 10.1038/SJ.ONC.1202984