Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1565-1573 |
| Number of pages | 9 |
| Journal | Laboratory Investigation |
| Volume | 81 |
| Issue number | 11 |
| Publication status | Published - 2001 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
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Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells. / Takashima, Hirotoshi; Matsumoto, Yusuke; Matsubara, Nagahide; Shirakawa, Yasuhiro; Kawashima, Ryuichi; Tanino, Motohiko; Itou, Sachio; Isozaki, Hiroshi; Oouchida, Mamoru; Meltzer, Stephen J.; Shimizu, Kenji; Tanaka, Noriaki.
In: Laboratory Investigation, Vol. 81, No. 11, 2001, p. 1565-1573.Research output: Contribution to journal › Article
}
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 - Itou, Sachio
AU - Isozaki, Hiroshi
AU - Oouchida, Mamoru
AU - Meltzer, Stephen J.
AU - Shimizu, Kenji
AU - Tanaka, Noriaki
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
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 -