TY - JOUR
T1 - The bone morphogenetic protein pathway is active in human colon adenomas and inactivated in colorectal cancer
AU - Kodach, Liudmila L.
AU - Bleuming, Sylvia A.
AU - Musler, Alex R.
AU - Peppelenbosch, Maikel P.
AU - Hommes, Daniel W.
AU - Van Den Brink, Gijs R.
AU - Van Noesel, Carel J M
AU - Offerhaus, G. Johan A
AU - Hardwick, James C H
PY - 2008/1/15
Y1 - 2008/1/15
N2 - 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
AB - 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
KW - Adenoma-carcinoma sequence
KW - Bone morphogenetic protein receptors
KW - Colorectal cancer
KW - SMAD proteins
KW - Tissue microarray
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U2 - 10.1002/cncr.23160
DO - 10.1002/cncr.23160
M3 - Article
C2 - 18008360
AN - SCOPUS:38049029612
SN - 0008-543X
VL - 112
SP - 300
EP - 306
JO - Cancer
JF - Cancer
IS - 2
ER -