TY - JOUR
T1 - Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX
AU - Ishii, Hideshi
AU - Mimori, Koshi
AU - Vecchione, Andrea
AU - Sutheesophon, Krittaya
AU - Fujiwara, Toshiyoshi
AU - Mori, Masaki
AU - Furukawa, Yusuke
N1 - Funding Information:
We thank Dr. Ta-Jen Liu, University of Texas, M.D. Anderson Cancer Center, USA, for giving adenoviral E2F-1 vector, Dr. Kay Huebner, Thomas Jefferson University, USA, for anti-Wwox antibody, and Miss Taeko Inageta for technical assistance. This work was supported in part by the research funds from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Kato Memorial Bioscience Foundation, the Chiyoda Health Foundation, the Suzuken Memorial Foundation, and the Japanese Leukemia Research Foundation.
PY - 2004/4/16
Y1 - 2004/4/16
N2 - The expression of two tumor suppressor genes, fragile histidine triad (FHIT) and WW domain containing oxidoreductase (WWOX), encompassing common chromosome fragile regions, FRA3B at 3p14.2 and FRA16D at 16q23, is altered in many epithelial tumors. Since DNA sequence search shows that the FHIT gene has the E2F-1 recognition site in 5′ region, which regulates cell cycle, we tested the effect of E2F-1 overexpression in tumor cells. Ectopic E2F-1 expression led to an increase of Fhit and Wwox expression in allele remaining tumor cells and resulted in induction of apoptosis. Reporter assay showed that the E2F-1 site in FHIT 5′ region was involved in the down-stream transcription after exogenous E2F-1 introduction. Chromatin immunoprecipitation detected exogenous E2F-1 binding to the recognition site in FHIT 5′ region. The data suggest that E2F-1 overexpression plays a role in suppression of tumor, at least in part trough transcriptional regulation of FHIT and relevant activation of WWOX.
AB - The expression of two tumor suppressor genes, fragile histidine triad (FHIT) and WW domain containing oxidoreductase (WWOX), encompassing common chromosome fragile regions, FRA3B at 3p14.2 and FRA16D at 16q23, is altered in many epithelial tumors. Since DNA sequence search shows that the FHIT gene has the E2F-1 recognition site in 5′ region, which regulates cell cycle, we tested the effect of E2F-1 overexpression in tumor cells. Ectopic E2F-1 expression led to an increase of Fhit and Wwox expression in allele remaining tumor cells and resulted in induction of apoptosis. Reporter assay showed that the E2F-1 site in FHIT 5′ region was involved in the down-stream transcription after exogenous E2F-1 introduction. Chromatin immunoprecipitation detected exogenous E2F-1 binding to the recognition site in FHIT 5′ region. The data suggest that E2F-1 overexpression plays a role in suppression of tumor, at least in part trough transcriptional regulation of FHIT and relevant activation of WWOX.
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U2 - 10.1016/j.bbrc.2004.02.159
DO - 10.1016/j.bbrc.2004.02.159
M3 - Article
C2 - 15044096
AN - SCOPUS:1642416689
SN - 0006-291X
VL - 316
SP - 1088
EP - 1093
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -