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

Soon Young Shin, Jesang 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

Research output: Contribution to journalArticle

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

Fingerprint

Fibroblasts
Rats
Genes
Growth
Tumors
src Homology Domains
Transcription
Cycloheximide
phospholipase C1
Ternary Complex Factors
Serum Response Element
Thrombospondin 1
Neoplasms
Protein Synthesis Inhibitors
Plasminogen Activator Inhibitor 1
Reporter Genes
Epidermal Growth Factor
Gene expression
Base Pairing
Modulators

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Shin, Soon Young ; Ko, Jesang ; Chang, Jong Soo ; Min, Do Sik ; Choi, Chan ; Bae, Sun Sik ; Kim, Myung Jong ; Hyun, Dae Sung ; Kim, Jung Hye ; Han, Mi Young ; Kim, Young Ho ; Kim, Yong Sik ; Na, Doe Sun ; Suh, Pann Ghill ; Lee, Young Han. / Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts. In: FASEB Journal. 2002 ; Vol. 16, No. 12. pp. 1504-1514.
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title = "Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts",
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.",
author = "Shin, {Soon Young} and Jesang Ko and Chang, {Jong Soo} and Min, {Do Sik} and Chan Choi and Bae, {Sun Sik} and Kim, {Myung Jong} and Hyun, {Dae Sung} and Kim, {Jung Hye} and Han, {Mi Young} and Kim, {Young Ho} and Kim, {Yong Sik} and Na, {Doe Sun} and Suh, {Pann Ghill} and Lee, {Young Han}",
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Shin, SY, Ko, J, Chang, JS, Min, DS, Choi, C, Bae, SS, Kim, MJ, Hyun, DS, Kim, JH, Han, MY, Kim, YH, Kim, YS, Na, DS, Suh, PG & Lee, YH 2002, 'Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts', FASEB Journal, vol. 16, no. 12, pp. 1504-1514. https://doi.org/10.1096/fj.02-0022com

Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts. / Shin, Soon Young; Ko, Jesang; Chang, Jong Soo; Min, Do Sik; Choi, Chan; Bae, Sun Sik; Kim, Myung Jong; Hyun, Dae Sung; Kim, Jung Hye; Han, Mi Young; Kim, Young Ho; Kim, Yong Sik; Na, Doe Sun; Suh, Pann Ghill; Lee, Young Han.

In: FASEB Journal, Vol. 16, No. 12, 01.10.2002, p. 1504-1514.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts

AU - Shin, Soon Young

AU - Ko, Jesang

AU - Chang, Jong Soo

AU - Min, Do Sik

AU - Choi, Chan

AU - Bae, Sun Sik

AU - Kim, Myung Jong

AU - Hyun, Dae Sung

AU - Kim, Jung Hye

AU - Han, Mi Young

AU - Kim, Young Ho

AU - Kim, Yong Sik

AU - Na, Doe Sun

AU - Suh, Pann Ghill

AU - Lee, Young Han

PY - 2002/10/1

Y1 - 2002/10/1

N2 - 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.

AB - 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.

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