Activation of Notch signaling in human colon adenocarcinoma

作者：Reedijk Michael; Odorcic Silvia; Zhang Hui; Chetty Runjan; Tennert Carsten; Dickson Brendan C; Lockwood Gina; Gallinger Steven; Egan Sean E^*

来源：International Journal of Oncology, 2008, 33(6): 1223-1229.

DOI：10.3892/ijo_00000112

• Notch
• Hes1
• colon cancer
• signaling
• prognosis

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 APC(Min) 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 APC(Min) mouse, may respond to anti-Notch therapeutic regimes.

• 出版日期2008-12