MUC5AC mucin gene regulation in pancreatic cancer cells

  • Authors:
    • Shingo Kato
    • Ryota Hokari
    • Suzanne Crawley
    • James Gum
    • Dae-Ho Ahn
    • Jong-Woo Kim
    • Sung-Won Kwon
    • Soichiro Miura
    • Carol B. Basbaum
    • Young S. Kim
  • View Affiliations

  • Published online on: July 1, 2006     https://doi.org/10.3892/ijo.29.1.33
  • Pages: 33-40
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Abstract

MUC5AC is a secretory mucin normally expressed by the surface mucous cells of the human stomach and in the bronchial tract. It is absent from normal pancreas, but de novo expression of this mucin occurs in early-stage pancreatic intraepithelial neoplasias and in the invasive ductal adenocarcinoma of the pancreas, prompting this study of MUC5AC gene regulation in pancreatic cancer cells. Promoter deletion constructs and EMSA studies revealed that transcription factors Sp1 and AP-1 are both involved in basal transcription of the MUC5AC gene. Phorbol 12-myrisate 13-acetate (PMA) increased MUC5AC mRNA expression and transcriptional activities of MUC5AC promoter-reporter deletion constructs containing AP-1 consensus sites. EMSA studies showed that Fos/Jun binding to putative AP-1 sites is increased by PMA treatment. Western blot analysis showed that ERK, JNK and p38 are all activated by PMA treatment in SW1990 cells. Inhibitors of mitogen-activated protein/extracellular signal regulated kinase (MEK), such as ERK inhibitor PD98059 and JNK inhibitors dicumarol and SP60015, but not p38 inhibitor SB203580, inhibited PMA-induced MUC5AC reporter activity. Our studies indicate that Sp1 is involved in basal MUC5AC promoter activity while AP-1 is involved in basal and PMA-induced MUC5AC promoter activation in pancreatic cancer cells. Furthermore, PMA-induced MUC5AC gene transcription appears to be mediated by activating Sp1, PKC/ERK/AP-1 and PKC/JNK/AP-1 pathways.

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July 2006
Volume 29 Issue 1

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

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Spandidos Publications style
Kato S, Hokari R, Crawley S, Gum J, Ahn D, Kim J, Kwon S, Miura S, Basbaum CB, Kim YS, Kim YS, et al: MUC5AC mucin gene regulation in pancreatic cancer cells. Int J Oncol 29: 33-40, 2006.
APA
Kato, S., Hokari, R., Crawley, S., Gum, J., Ahn, D., Kim, J. ... Kim, Y.S. (2006). MUC5AC mucin gene regulation in pancreatic cancer cells. International Journal of Oncology, 29, 33-40. https://doi.org/10.3892/ijo.29.1.33
MLA
Kato, S., Hokari, R., Crawley, S., Gum, J., Ahn, D., Kim, J., Kwon, S., Miura, S., Basbaum, C. B., Kim, Y. S."MUC5AC mucin gene regulation in pancreatic cancer cells". International Journal of Oncology 29.1 (2006): 33-40.
Chicago
Kato, S., Hokari, R., Crawley, S., Gum, J., Ahn, D., Kim, J., Kwon, S., Miura, S., Basbaum, C. B., Kim, Y. S."MUC5AC mucin gene regulation in pancreatic cancer cells". International Journal of Oncology 29, no. 1 (2006): 33-40. https://doi.org/10.3892/ijo.29.1.33