TY - JOUR
T1 - Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells
AU - Takashima, Hirotoshi
AU - Matsumoto, Yusuke
AU - Matsubara, Nagahide
AU - Shirakawa, Yasuhiro
AU - Kawashima, Ryuichi
AU - Tanino, Motohiko
AU - Ito, Sachio
AU - Isozaki, Hiroshi
AU - Ouchida, Mamoru
AU - Meltzer, Stephen J.
AU - Shimizu, Kenji
AU - Tanaka, Noriaki
N1 - Funding Information:
This work was supported by a Grant-in Aid from the Japanese Ministry of Education, Science, Sports and Culture of Japan (11671237, 11671240, and 10470040), and National Institutes of Health Grants CA85069, DK47717, CA77057, CA78843, and the Medical Research Service, Department of Veterans Affairs. Address reprint requests to: Dr. Nagahide Matsubara, Department of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail: nagamb@cc.okayama-u.ac.jp
PY - 2001
Y1 - 2001
N2 - E2F is a family of transcription factors implicated in the regulation of gene expression required for progression through the G1-S transition. We have previously detected tumor-specific mutations at a trinucleotide repeat coding sequence of E2F-4 gene in a subset of human sporadic colorectal cancers. The purpose of this study was to investigate the potential functional consequences of these E2F-4 mutations. We transfected NIH3T3 fibroblasts with expression constructs containing wild-type as well as mutant E2F-4 cDNA, and the effect of the E2F-4 mutations on proliferation was examined. Alteration in transactivation of the E2F consensus promoter sequence was also examined by transient cotransfection of a E2F-4 with a DP-2 construct into cultured human cells. Transfected cell clones overexpressing mutant E2F-4 grew more rapidly and showed higher proliferative activity by increased immunohistochemical staining for proliferating cell nuclear antigen (PCNA). All three mutant forms of E2F-4 showed elevated transactivation of the E2F consensus promoter sequence. Thus, expression of mutant E2F-4s confers a growth advantage in vivo, and this effect may be related to the acquisition of a neoplastic phenotype.
AB - E2F is a family of transcription factors implicated in the regulation of gene expression required for progression through the G1-S transition. We have previously detected tumor-specific mutations at a trinucleotide repeat coding sequence of E2F-4 gene in a subset of human sporadic colorectal cancers. The purpose of this study was to investigate the potential functional consequences of these E2F-4 mutations. We transfected NIH3T3 fibroblasts with expression constructs containing wild-type as well as mutant E2F-4 cDNA, and the effect of the E2F-4 mutations on proliferation was examined. Alteration in transactivation of the E2F consensus promoter sequence was also examined by transient cotransfection of a E2F-4 with a DP-2 construct into cultured human cells. Transfected cell clones overexpressing mutant E2F-4 grew more rapidly and showed higher proliferative activity by increased immunohistochemical staining for proliferating cell nuclear antigen (PCNA). All three mutant forms of E2F-4 showed elevated transactivation of the E2F consensus promoter sequence. Thus, expression of mutant E2F-4s confers a growth advantage in vivo, and this effect may be related to the acquisition of a neoplastic phenotype.
UR - http://www.scopus.com/inward/record.url?scp=0035175005&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035175005&partnerID=8YFLogxK
U2 - 10.1038/labinvest.3780370
DO - 10.1038/labinvest.3780370
M3 - Article
C2 - 11706064
AN - SCOPUS:0035175005
VL - 81
SP - 1565
EP - 1573
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 11
ER -
