The bone morphogenetic protein pathway is active in human colon adenomas and inactivated in colorectal cancer

Liudmila L. Kodach, Sylvia A. Bleuming, Alex R. Musler, Maikel P. Peppelenbosch, Daniel W. Hommes, Gijs R. Van Den Brink, Carel J M Van Noesel, G. Johan A Offerhaus, James C H Hardwick

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

BACKGROUND. Transforming growth factor β (TGFβ) is important in colorectal cancer (CRC) progression. Bone morphogenetic proteins (BMPs), a subgroup within the TGFβ superfamily, recently also have been implicated in CRC, but their precise role in CRC has yet to be investigated. METHODS. The authors used a tissue microarray and immunohistochemistry of BMP receptors and signal transduction elements in adenomas and CRC specimens to elucidate the role of BMP signaling in CRC carcinogenesis. RESULTS. The adenoma specimens expressed all 3 BMP receptors (BMPRs) (BMPR type 1a [BMPR1a], BMPR1b, and BMPR2) and expressed SMAD family member 4 (SMAD4); and 20 of 22 adenomas (90.9%) exhibited active BMP signaling, as determined by nuclear phosphorylated SMAD 1,5,8 (pSMAD1,5,8) expression. In contrast, pSMAD1,5,8 nuclear staining was present in 5 CRC specimens (22.7%) but was lost in 17 CRC specimens (77.3%; cancer vs adenoma; P

Original languageEnglish (US)
Pages (from-to)300-306
Number of pages7
JournalCancer
Volume112
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

Keywords

  • Adenoma-carcinoma sequence
  • Bone morphogenetic protein receptors
  • Colorectal cancer
  • SMAD proteins
  • Tissue microarray

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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