✦ LIBER ✦

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

✍ Scribed by 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

Publisher: John Wiley and Sons
Year: 2008
Tongue: English
Weight: 273 KB
Volume: 112
Category: Article
ISSN: 0008-543X
DOI: 10.1002/cncr.23160

No coin nor oath required. For personal study only.

✦ Synopsis

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 SMAD1,5,8 (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 < .0001). The earliest loss of pSMAD1,5,8 nuclear staining was detected in regions of high‐grade dysplasia/carcinoma in situ within adenomas. CRCs showed frequent loss of BMPR2 (P < .0001) and SMAD4 (P < .01) compared with adenomas. Negative expression of BMPR2 was observed more frequently in earlier stage cancers (Dukes stage B) than in advanced cancers (Dukes stage C; P < .05).

CONCLUSIONS.

Taken together, the current results indicated that loss of BMP signaling correlates tightly with progression of adenomas to cancer and occurs relatively early during cancer progression. Cancer 2008. © 2007 American Cancer Society.

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