Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells

Hirotoshi Takashima, Yusuke Matsumoto, Nagahide Matsubara, Yasuhiro Shirakawa, Ryuichi Kawashima, Motohiko Tanino, Sachio Itou, Hiroshi Isozaki, Mamoru Oouchida, Stephen J. Meltzer, Kenji Shimizu, Noriaki Tanaka

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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 languageEnglish
Pages (from-to)1565-1573
Number of pages9
JournalLaboratory Investigation
Volume81
Issue number11
Publication statusPublished - 2001

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Transcriptional Activation
Consensus Sequence
Mutation
Trinucleotide Repeats
Proliferating Cell Nuclear Antigen
Gene Expression Regulation
Colorectal Neoplasms
Cultured Cells
Transcription Factors
Complementary DNA
Clone Cells
Fibroblasts
Staining and Labeling
Phenotype
Growth
Genes
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Takashima, H., Matsumoto, Y., Matsubara, N., Shirakawa, Y., Kawashima, R., Tanino, M., ... Tanaka, N. (2001). Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells. Laboratory Investigation, 81(11), 1565-1573.

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 journalArticle

Takashima, H, Matsumoto, Y, Matsubara, N, Shirakawa, Y, Kawashima, R, Tanino, M, Itou, S, Isozaki, H, Oouchida, M, Meltzer, SJ, Shimizu, K & Tanaka, N 2001, 'Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells', Laboratory Investigation, vol. 81, no. 11, pp. 1565-1573.
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. / Effect of naturally occurring E2F-4 alterations on transcriptional activation and proliferation in transfected cells. In: Laboratory Investigation. 2001 ; Vol. 81, No. 11. pp. 1565-1573.
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