Negative regulatory role of overexpression of PLC gamma 1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts.
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 Cgamma1 (PLCgamma1) is overexpressed in some tumors, and its overexpression causes anchorage-independent growth. Here we report that overexpression of PLCgamma1 and SH2-SH3 domain of PLCgamma1 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 PLCgamma1-3Y1 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 PLCgamma1-3Y1 cells. Pretreatment with the protein synthesis inhibitor cycloheximide (CHX) partially abrogated the serum-induced suppression of Egr-1 transcription in PLCgamma1-3Y1 cells, suggesting that a CHX-sensitive factor(s) is involved in the suppression of Egr-1 transcription in PLCgamma1-3Y1 cells. Our results demonstrated that overexpression of PLCgamma1 functions as a negative modulator of the tumor suppressor Egr-1 gene expression, possibly through inhibition of Elk-1-dependent transcriptional activity.
Shin
Soon Young
SY
Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea 705-717.
Ko
Jesang
J
Chang
Jong-Soo
JS
Min
Do Sik
DS
Choi
Chan
C
Bae
Sun Sik
SS
Kim
Myung Jong
MJ
Hyun
Dae Sung
DS
Kim
Jung-Hye
JH
Han
Mi Young
MY
Kim
Young-Ho
YH
Kim
Yong Sik
YS
Na
Doe Sun
DS
Suh
Pann-Ghill
PG
Lee
Young Han
YH
D000818:Animals; D002460:Cell Line; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051966:Phospholipase C gamma; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D050807:ets-Domain Protein Elk-1; D018909:src Homology Domains / Q000235:genetics
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; C494112:ELK1 protein, human; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C494114:Elk1 protein, rat; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D003513:Cycloheximide; D010738:Type C Phospholipases; D051966:Phospholipase C gamma