Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts

Soon Young Shin, Je Sang Ko, Jong Soo Chang, Do Sik Min, Chan Choi, Sun Sik Bae, Myung Jong Kim, Dae Sung Hyun, Jung Hye Kim, Mi Young Han, Young Ho Kim, Yong Sik Kim, Doe Sun Na, Pann Ghill Suh, Young Han Lee

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11 Citations (Scopus)

Abstract

The early growth response 1 (Egr-1) gene product is a transcription factor that functions as an oikis factor. Loss of Egr-1 expression is closely associated with tumor formation. Phospholipase Cγ1 (PLCγ1) is overexpressed in some tumors, and its overexpression causes anchorage-independent growth. Here we report that overexpression of PLCγ1 and SH2-SH3 domain of PLCγ1 decreased induction of Egr-1 and the Egr-1-regulated genes TSP-1 and PAI-1. Results from the nuclear run-on assay and transfection experiment with the proximal 455 base pair region of the Egr-1 promoter (-454 to +1) showed that Egr-1 transcriptional activity was suppressed in PLCγ1-3Y1 cells whereas decay of Egr-1 mRNA was similar in both cell lines. Serum response element- and ternary complex factor Elk-1-mediated transcriptional activation of the reporter gene in response to EGF were also inhibited in PLCγ1-3Y1 cells. Pretreatment with the protein synthesis inhibitor cycloheximide (CHX) partially abrogated the serum-induced suppression of Egr-1 transcription in PLCγ1-3Y1 cells, suggesting that a CHX-sensitive factor(s) is involved in the suppression of Egr-1 transcription in PLCγ1-3Y1 cells. Our results demonstrated that overexpression of PLCγ1 functions as a negative modulator of the tumor suppressor Egr-1 gene expression, possibly through inhibition of Elk-1-dependent transcriptional activity.

Original languageEnglish
Pages (from-to)1504-1514
Number of pages11
JournalFASEB Journal
Volume16
Issue number12
DOIs
Publication statusPublished - 2002 Oct 1
Externally publishedYes

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Keywords

  • Egr-1
  • PLCγ1 overexpression
  • Tumor suppressor

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Shin, S. Y., Ko, J. S., Chang, J. S., Min, D. S., Choi, C., Bae, S. S., Kim, M. J., Hyun, D. S., Kim, J. H., Han, M. Y., Kim, Y. H., Kim, Y. S., Na, D. S., Suh, P. G., & Lee, Y. H. (2002). Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts. FASEB Journal, 16(12), 1504-1514. https://doi.org/10.1096/fj.02-0022com