Mutated ras induced PLD1 gene expression through increased Sp1 transcription factor.

Siqiang Gao, Masashi Murakami, Hiromi Ito, Ayako Furuhata, Kayo Yoshida, Yoko Tagawa, Kazumi Hagiwara, Akira Takagi, Tetsuhito Kojima, Motoshi Suzuki, Yoshiko Banno, Yoshinori Nozawa, Takashi Murate

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8 Citations (Scopus)

Abstract

The underlying mechanisms of oncogene-induced phospholipase D (PLD) activation have not been fully elucidated. The effect of the mutated-ras on PLD mRNA was examined using colon cancer cell lines as well as mock- and mutated ras-transfected NIH3T3 cells. Ras-mutation and activation were correlated, and cells with enhanced ras-activation showed increased PLD1 mRNA and protein. Analysis of the 5' PLD1 promoter using a representative cell line, DLD-1 and also mutated ras-NIH3T3, showed one Sp1-site as the important ras-responsible motif. Spl inhibition with mithramycin A and Spl siRNA inhibited PLD1 protein expression and its promoter activity. Sp1 but not Sp3 protein level and increased Sp1-motif binding activity were correlated with ras activation. Furthermore, overexpression of Sp1 in drosophila SL2 cells lacking Sp family proteins increased PLD1 promoter activity. EMSA and chromatin immunoprecipitation assay confirmed the importance of Sp1 protein binding to the Sp1-motif in ras-induced PLD1 mRNA expression.

Original languageEnglish
Pages (from-to)127-136
Number of pages10
JournalNagoya journal of medical science
Volume71
Issue number3-4
Publication statusPublished - 09-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Gao, S., Murakami, M., Ito, H., Furuhata, A., Yoshida, K., Tagawa, Y., Hagiwara, K., Takagi, A., Kojima, T., Suzuki, M., Banno, Y., Nozawa, Y., & Murate, T. (2009). Mutated ras induced PLD1 gene expression through increased Sp1 transcription factor. Nagoya journal of medical science, 71(3-4), 127-136.