Expression of connective tissue growth factor in pancreatic cancer cell lines

  • Authors:
    • Sungwon Kwon
    • Xander Munroe
    • Suzanne C. Crawley
    • Hwa Young Lee
    • Suzanne Spong
    • Douglass Bradham
    • James R. Gum
    • Marvin H. Sleisenger
    • Young S. Kim
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/ijo.31.4.693
  • Pages: 693-703
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Abstract

Connective tissue growth factor (CTGF/CCN2) is thought to play a role in normal wound repair and bone remodeling, but also promotes fibrosis in several disease processes including diabetic nephropathy, sclerodoma and pancreatitis. A contribution to desmoplasia associated with pancreatic cancer progression has also been proposed. CTGF is induced by TGFβ in diverse cell types, but TGFβ receptor mediated signaling is impaired in pancreatic cancers and cell lines, usually due to DPC4/Smad4 mutations which arise during the later stages of intraepithelial neoplastic progression. Therefore, in order to define signaling pathways that mediate basal and TGFβ-induced CTGF expression in normal and transformed cells, we compared CTGF gene regulation in pancreatic cancer cells and fibroblasts by measuring the effects of small molecule inhibitors and dominant negative mutants of signaling proteins on CTGF promoter reporter activity, message, and protein expression. We determined that the previously identified TEF-1 cis element is essential for CTGF promoter reporter activity in pancreatic cancer cell lines. Whereas p38 mediated CTGF induction by TGFβ in fibroblasts, MEK/ERK signaling mediated TGFβ-induced CTGF expression in pancreatic cancer cells and was also responsible for basal CTGF expression in pancreatic cancer cell lines with defective Smad signaling. Since activating Ras mutations occur in the earliest stages of pancreatic cancer, CTGF may be induced independent of Smad4 in pancreatic cancer cells.

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October 2007
Volume 31 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kwon S, Munroe X, Crawley SC, Lee HY, Spong S, Bradham D, Gum JR, Sleisenger MH and Kim YS: Expression of connective tissue growth factor in pancreatic cancer cell lines. Int J Oncol 31: 693-703, 2007
APA
Kwon, S., Munroe, X., Crawley, S.C., Lee, H.Y., Spong, S., Bradham, D. ... Kim, Y.S. (2007). Expression of connective tissue growth factor in pancreatic cancer cell lines. International Journal of Oncology, 31, 693-703. https://doi.org/10.3892/ijo.31.4.693
MLA
Kwon, S., Munroe, X., Crawley, S. C., Lee, H. Y., Spong, S., Bradham, D., Gum, J. R., Sleisenger, M. H., Kim, Y. S."Expression of connective tissue growth factor in pancreatic cancer cell lines". International Journal of Oncology 31.4 (2007): 693-703.
Chicago
Kwon, S., Munroe, X., Crawley, S. C., Lee, H. Y., Spong, S., Bradham, D., Gum, J. R., Sleisenger, M. H., Kim, Y. S."Expression of connective tissue growth factor in pancreatic cancer cell lines". International Journal of Oncology 31, no. 4 (2007): 693-703. https://doi.org/10.3892/ijo.31.4.693