Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines

Shin Hamada, Kennichi Satoh, Morihisa Hirota, Wataru Fujibuchi, Atsushi Kanno, Jun Umino, Hiromichi Ito, Akihiko Satoh, Kazuhiro Kikuta, Kiyoshi Kume, Atsushi Masamune, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

We previously reported that bone morphogenetic protein (BMP)-4 induces epithelial-mesenchymal transition in a pancreatic cancer cell line. To further investigate the detailed molecular mechanism of BMP action in pancreatic cancer, we carried out comprehensive microarray analysis in Panc-1 cells. The microarray analysis elucidated novel BMP target genes, and among them, the calcium-binding protein S100P was identified as an upregulated gene. S100P induction by BMP4 was confirmed by real-time reverse transcription-polymerase chain reaction and western blot analysis in Panc-1 and HPDE cells. Short interfering RNA-based knockdown of S100P expression sufficiently repressed BMP4-induced cell migration in Panc-1 cells. Because Panc-1 and HPDE cells express wild-type Smad4, we hypothesized that Smad4 might be indispensable for S100P induction by BMP4. S100P induction by BMP4 was not observed in the Smad4-null cell line BxPC3, and was sufficiently attenuated in short interfering RNA-based Smad4-knockdown Panc-1 cells. Interestingly, detailed promoter analysis revealed that upregulation of S100P by BMP4 was independent of the Smad-binding element, indicating that an additional unknown downstream factor of the Smad4-dependent pathway is necessary for this induction. These findings are the first of their kind, and this Smad4-dependent regulation of S100P by BMP signaling might explain the migratory mechanism of cancer cells, which is still unknown.

Original languageEnglish
Pages (from-to)103-110
Number of pages8
JournalCancer science
Volume100
Issue number1
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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