| Expression of the calcium-binding protein S100P is regulated by bone morphogenetic protein in pancreatic duct epithelial cell lines. | |
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MedLine Citation:
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PMID: 19018761 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Shin Hamada; Kennichi Satoh; Morihisa Hirota; Wataru Fujibuchi; Atsushi Kanno; Jun Umino; Hiromichi Ito; Akihiko Satoh; Kazuhiro Kikuta; Kiyoshi Kume; Atsushi Masamune; Tooru Shimosegawa |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-10-23 |
Journal Detail:
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Title: Cancer science Volume: 100 ISSN: 1349-7006 ISO Abbreviation: Cancer Sci. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-08 Completed Date: 2009-01-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: England |
Other Details:
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Languages: eng Pagination: 103-10 Citation Subset: IM |
Affiliation:
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Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Bone Morphogenetic Protein 4
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pharmacology* Calcium-Binding Proteins / genetics* Carcinoma, Pancreatic Ductal / metabolism* Cell Line, Tumor Gene Expression Regulation, Neoplastic / drug effects* Humans Neoplasm Proteins / genetics* Oligonucleotide Array Sequence Analysis Pancreatic Neoplasms / metabolism*, pathology Smad4 Protein / physiology |
| Chemical | |
Reg. No./Substance:
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0/BMP4 protein, human; 0/Bone Morphogenetic Protein 4; 0/Calcium-Binding Proteins; 0/Neoplasm Proteins; 0/S100P protein, human; 0/SMAD4 protein, human; 0/Smad4 Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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