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Multicenter Study
. 2008 Dec;33(6):1223-9.
doi: 10.3892/ijo_00000112.

Activation of Notch signaling in human colon adenocarcinoma

Michael Reedijk  1 , Silvia Odorcic, Hui Zhang, Runjan Chetty, Carsten Tennert, Brendan C Dickson, Gina Lockwood, Steven Gallinger, Sean E Egan
Affiliations
Multicenter Study

Activation of Notch signaling in human colon adenocarcinoma

Michael Reedijk et al. Int J Oncol. 2008 Dec.

Abstract

Notch and Wnt signaling function together to regulate colonic progenitor cell division and differentiation. Studies in mice have also shown that Notch signaling is required for adenoma formation in response to elevated Wnt-pathway signaling that occurs in the APCMin mouse model of human adenomatous polyposis coli. We therefore used in situ hybridization to analyze expression of Notch ligands, receptors and fringe genes, as well as the Notch target gene, HES1, in human colorectal cancer (CRC). In a small cohort of tumors, JAGGED ligands, NOTCH1, LFNG and HES1 were expressed at levels similar to, or higher than, levels observed in the crypt. To explore the possibility that Notch signaling may play a quantitative role in human CRC we next analyzed HES1 mRNA expression in 130 tumors, each associated with outcome data. The vast majority of these tumors expressed HES1, although at varying levels. Absolute expression levels did not correlate with patient survival. These results establish that JAG ligands and NOTCH1, as well as Notch receptor activation are consistent features of human CRC and support the notion that many of these tumors, like the APCMin mouse, may respond to anti-Notch therapeutic regimes.

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Figures

Figure 1
Figure 1
Expression of Notch ligands, receptors and fringes in human CRC. In situ hybridization using antisense probes for JAG1 (A,A'), JAG2 (B,B'), NOTCH1 (C,C'), and LFNG (D,D'). Bright field images are shown on the left (A–-D) and dark filed images on the right (A'–D'). High level Notch ligand, receptor and Fringe mRNA expression occurs in some invasive adenenocarcinomas of the colon. Scale bars in each panel are 200 microns in length.
Figure 2
Figure 2
Kaplan-Merier curve shows no relationship between high level HES1 gene expression and survival in patients with colorectal cancer.
See this image and copyright information in PMC

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