Different transcriptional strategies for ccn2/ctgf gene induction between human chondrocytic and breast cancer cell lines

Takanori Eguchi, Satoshi Kubota, Kazumi Kawata, Yoshiki Mukudai, Toshihiro Ohgawara, Kohei Miyazono, Kyouji Nakao, Seiji Kondo, Masaharu Takigawa

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Connective tissue growth factor (CTGF/CCN2) plays a critical role in endochondral bone formation; however, CCN2 also promotes angiogenesis and bone metastasis in breast cancer. Chondrocytic HCS-2/8 cells and breast cancer MDA231 cells produce over 6 times more CCN2 than any other cell type. In this study, we demonstrate that these cell lines employ different transcriptional strategies for ccn2 gene induction. Four tandem copies of the dominant transcriptional enhancer in chondrocytes (4 × TRENDIC) were chimerically connected to an SV40 promoter-luciferase construct and subsequently analyzed. The enhancement of the promoter activity by 4 × TRENDIC was greater in the HCS-2/8 cells (7-fold) than in the other 4 cell lines (3-4 fold). The TRENDIC-binding protein complex was detected at a higher signal in the HCS-2/8 cells than in the other cell lines. In addition, the HCS-2/8 nuclear factors strongly targeted not only TRENDIC, but also the previously reported basal control element and a novel enhancer element in the ccn2 promoter. In contrast, high-level ccn2 gene induction in MDA231 cells was largely dependent on Smad signaling through the Smad-binding element in the ccn2 promoter. Based on these results, we propose a model of differential transcription of the ccn2 gene between the chondrocytic cell line and the breast cancer cell line, and therefore imply that these cells utilize distinct transcriptional strategies to obtain the enhanced CCN2 production that is not observed in other types of cells.

Original languageEnglish
Pages (from-to)278-288
Number of pages11
JournalBiochimie
Volume89
Issue number3
DOIs
Publication statusPublished - Mar 1 2007

Keywords

  • Bone metastasis in breast cancer
  • CCN family
  • CTGF
  • Chondrocytes
  • Endochondral ossification
  • TRENDIC

ASJC Scopus subject areas

  • Biochemistry

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