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Negative regulatory role of overexpression of PLCγ1in the expression of early growth response 1 gene in rat 3Y1 fibroblasts
Author(s) -
Shin Soon Young,
Ko Jesang,
Chang JongSoo,
Min Do Sik,
Choi Chan,
Bae Sun Sik,
Kim Myung Jong,
Hyun Dae Sung,
Kim JungHye,
Han Mi Young,
Kim YoungHo,
Kim Yong Sik,
Na Doe Sun,
Suh PannGhill,
Lee Young Han
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0022com
Subject(s) - microbiology and biotechnology , transfection , biology , transcription (linguistics) , serum response element , transcription factor , reporter gene , gene expression , gene , cancer research , chemistry , serum response factor , philosophy , biochemistry , linguistics
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.—Shin, S. Y., Ko, J., 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. Negative regulatory role of overexpression of PLCγ1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts. FASEB J . 16, 1504–1514 (2002)