Bone Morphogenetic Protein 2 Is Expressed by, and Acts Upon, Mature Epithelial Cells in the Colon

James C H Hardwick, Gijs R. Van Den Brink, Sylvia A. Bleuming, Isabel Ballester, Jan M H Van Den Brande, Josbert J. Keller, G. Johan A Offerhaus, Sander J H Van Deventer, Maikel P. Peppelenbosch

Research output: Contribution to journalArticle

Abstract

Background & Aims: The recent findings of bone morphogenetic protein (BMP) receptor la mutations in juvenile polyposis and frequent Smad4 mutations in colon cancer suggest a role for BMPs in the colonic epithelium and colon cancer. We investigated the role of BMP2 in the colon. Methods: We assessed BMP receptor expression in cell lines using the reverse-transcribed polymerase chain reaction and immunoblotting. We investigated the effect of BMP2 on cell lines using the MTT assay and by immunoblotting for markers of differentiation, proliferation, and apoptosis. We assessed the expression of BMP2, its receptors, and signal transduction elements in mouse and human colon tissue using immunohistochemistry. We also investigated the effect of the BMP antagonist noggin in vivo in mice by assessing colon tissue with immunohistochemistry and immunoblotting. Finally, we investigated the expression of BMP2 in microadenomas from familial adenomatous polyposis patients. Results: BMP receptors (BMPR) Ia, BMPR Ib, and BMPR Il are all expressed in colonic epithelial cell lines. BMP2 inhibits colonic epithelial cell growth in vitro, promoting apoptosis and differentiation and inhibiting proliferation. BMP2, BMPRIa, BMPRIb, BMPRIl, phosphorylated Smad1, and Smad4 are expressed predominantly in mature colonocytes at the epithelial surface in normal adult human and mouse colon. Noggin inhibits apoptosis and proliferation in mouse colonic epithelium in vivo. BMP2 expression is lost in the microadenomas of familial adenomatous polyposis patients. Conclusions: These data suggest that BMP2 acts as a tumor suppressor promoting apoptosis in mature colonic epithelial cells.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalGastroenterology
Volume126
Issue number1 SUPPL. 1
DOIs
StatePublished - Jan 2004
Externally publishedYes

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Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 2
Colon
Epithelial Cells
Immunoblotting
Colonic Neoplasms
Apoptosis
Adenomatous Polyposis Coli
Cell Line
Epithelium
Immunohistochemistry
Mutation
Bone Morphogenetic Proteins
Differentiation Antigens
Signal Transduction
Polymerase Chain Reaction
Growth
Neoplasms

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Hardwick, J. C. H., Van Den Brink, G. R., Bleuming, S. A., Ballester, I., Van Den Brande, J. M. H., Keller, J. J., ... Peppelenbosch, M. P. (2004). Bone Morphogenetic Protein 2 Is Expressed by, and Acts Upon, Mature Epithelial Cells in the Colon. Gastroenterology, 126(1 SUPPL. 1), 111-121. https://doi.org/10.1053/j.gastro.2003.10.067

Bone Morphogenetic Protein 2 Is Expressed by, and Acts Upon, Mature Epithelial Cells in the Colon. / Hardwick, James C H; Van Den Brink, Gijs R.; Bleuming, Sylvia A.; Ballester, Isabel; Van Den Brande, Jan M H; Keller, Josbert J.; Offerhaus, G. Johan A; Van Deventer, Sander J H; Peppelenbosch, Maikel P.

In: Gastroenterology, Vol. 126, No. 1 SUPPL. 1, 01.2004, p. 111-121.

Research output: Contribution to journalArticle

Hardwick, JCH, Van Den Brink, GR, Bleuming, SA, Ballester, I, Van Den Brande, JMH, Keller, JJ, Offerhaus, GJA, Van Deventer, SJH & Peppelenbosch, MP 2004, 'Bone Morphogenetic Protein 2 Is Expressed by, and Acts Upon, Mature Epithelial Cells in the Colon', Gastroenterology, vol. 126, no. 1 SUPPL. 1, pp. 111-121. https://doi.org/10.1053/j.gastro.2003.10.067
Hardwick JCH, Van Den Brink GR, Bleuming SA, Ballester I, Van Den Brande JMH, Keller JJ et al. Bone Morphogenetic Protein 2 Is Expressed by, and Acts Upon, Mature Epithelial Cells in the Colon. Gastroenterology. 2004 Jan;126(1 SUPPL. 1):111-121. https://doi.org/10.1053/j.gastro.2003.10.067
Hardwick, James C H ; Van Den Brink, Gijs R. ; Bleuming, Sylvia A. ; Ballester, Isabel ; Van Den Brande, Jan M H ; Keller, Josbert J. ; Offerhaus, G. Johan A ; Van Deventer, Sander J H ; Peppelenbosch, Maikel P. / Bone Morphogenetic Protein 2 Is Expressed by, and Acts Upon, Mature Epithelial Cells in the Colon. In: Gastroenterology. 2004 ; Vol. 126, No. 1 SUPPL. 1. pp. 111-121.
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