Abstract
Introduction
The significance of Notch1 expression in colorectal cancer has not been clearly described. We investigated the expression of Notch1 and its relationship with differentiation status and tumor (Union Internationale Contre le Cancer, UICC) stage using a series of 237 colorectal cancer samples with matched adjacent normal tissues and a series of 46 normal colorectal specimens.
Materials and Methods
Immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis were performed to assess the expression of Notch1.
Results
It was found that Notch1 was overexpressed in cancer tissues as compared with adjacent normal tissue and normal control tissues. Also, a tendency for increased expression was observed when going from well to poorly differentiated carcinomas, as well as going from UICC stage I to stage IV. With the differentiation of colon cancer cells, the expression of Notch1 decreased. To support this observation, colon cancer cell lines HT29 and SW620 were induced to differentiate in culture, and expression of Notch1 was investigated. A clear reduction of Notch1 expression was observed.
Conclusion
These results suggest that Notch1 expression correlated closely with colorectal cancer and may play an oncogenic role during colonic carcinogenesis.
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References
Sarfaty M, Wender R. How to increase colorectal cancer screening rates in practice. CA Cancer J Clin 2007;57:354–66. doi:10.3322/CA.57.6.354.
Ahmedin Jemal DVM, Siegel R, et al. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66.
Wang J. Current and future situation of colorectal carcinoma screening. J Dig Surg 2006;5:303–305.
Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005;434:843–850. doi:10.1038/nature03319.
Nathke IS. The adenomatous polyposis coli protein: the Achilles heel of the gut epithelium. Annu Rev Cell Dev Biol 2004;20:337–366. doi:10.1146/annurev.cellbio.20.012103.094541.
Greenwal I. LIN-12/Notch signaling: lessons from worms and flies. Genes Dev 1998;12:1751–62. doi:10.1101/gad.12.12.1751.
Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science 1999;284:770–6. doi:10.1126/science.284.5415.770.
Miele L, Osborne B. Arbiter of differentiation and death: Notch signaling meets apoptosis. J Cell Physiol 1999;181:393–409. doi:10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6.
Bigas A, Martin DI, Milner LA. Notch1 and Notch2 inhibit myeloid differentiation in response to different cytokines. Mol Cell Biol 1998;18:2324–33.
Mumm JS, Kopan R. Notch signaling: from the outside in. Dev Biol 2000;228:151–65. doi:10.1006/dbio.2000.9960.
Aster JC, Xu L, Karnell FG, et al. Essential roles for ankyrin repeat and transactivation domains in induction of T-cell leukemia by notch1. Mol Cell Biol 2000;20:7505–15. doi:10.1128/MCB.20.20.7505-7515.2000.
Bresnick EH, Chu J, Christensen HM, et al. Linking Notch signaling, chromatin remodeling, and T-cell leukemogenesis. J Cell Biochem Suppl 2000;Suppl 35:46–53. doi:10.1002/1097-4644(2000)79:35 + <46::AID-JCB1125>3.0.CO;2-5.
Hald J, Hjorth JP, German MS, et al. Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol 2003;260:426–437. doi:10.1016/S0012-1606(03)00326-9.
Jensen J, Heller RS, Funder-Nielsen T, et al. Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the Notch pathway in repression of premature differentiation. Diabetes 2000;49:163–176. doi:10.2337/diabetes.49.2.163.
Murtaugh LC, Stanger BZ, Kwan KM, et al. Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci U S A 2003;100:14920–14925. doi:10.1073/pnas.2436557100.
Apelqvist A, Li H, Sommer L, et al. Notch signalling controls pancreatic cell differentiation. Nature. 1999;400:877–81. doi:10.1038/23716.
Weijzen S, Rizzo P, Braid M, et al. Activation of Notch1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med 2002;8:979–86. doi:10.1038/nm754.
Nicolas M, Wolfer A, Raj K, et al. Notch1 functions as a tumor suppressor in mouse skin. Nat Genet 2003;33:416–21. doi:10.1038/ng1099.
Sriuranpong V, Borges MW, Ravi RK, et al. Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res 2001;61:3200–5.
Zlobin A, Jang M, Miele L. Toward the rational design of cell fate modifiers: Notch signaling as a target for novel biopharmaceuticals. Curr Pharm Biotechnol. 2000;1:83–106. doi:10.2174/1389201003379013.
Jang MS, Zlobin A, Kast WM, et al. Notch signaling as a target in multimodality cancer therapy. Curr Opin Mol Ther 2000;2:55–65.
Joutel A, Tournier-Lasserve E. Notch signalling pathway and human diseases. Semin Cell Dev Biol. 1998;9:619–25. doi:10.1006/scdb.1998.0261.
Jundt F, Anagnostopoulos I, Forster R, et al. Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood 2002;99:3398–403. doi:10.1182/blood.V99.9.3398.
Miele L, Osborne B. Arbiter of differentiation and death: Notch signaling meets apoptosis. J Cell Physiol. 1999;181:393–409. doi:10.1002/(SICI)1097-4652(199912)181:3<393::AID-JCP3>3.0.CO;2-6.
Brown RS, Wahl RL. Overexpression of Glut-1 glucose transporter in human breast cancer: an immunohistochemical study [J]. Cancer 1993;72:2979–2985. doi:10.1002/1097-0142(19931115)72:10<2979::AID-CNCR2820721020>3.0.CO;2-X.
Radtke F, Raj K. The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer 2003;3:756–67. doi:10.1038/nrc1186.
Ellisen LW, Bird J, West DC, et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 1991;66:649–661. doi:10.1016/0092-8674(91)90111-B.
Jundt F, Anagnostopoulos I, Forster R, et al. Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood 2002;99:3398–3403. doi:10.1182/blood.V99.9.3398.
Jundt F, Probsting KS, Anagnostopoulos I, et al. Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells. Blood 2004;103:3511–3515. doi:10.1182/blood-2003-07-2254.
Miele L. Notch signaling. Clin Cancer Res 2006;12:1074–1079. doi:10.1158/1078-0432.CCR-05-2570.
Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005;434:843–850. doi:10.1038/nature03319.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 30571803).
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Chu, D., Wang, W., Xie, H. et al. Notch1 Expression in Colorectal Carcinoma Determines Tumor Differentiation Status. J Gastrointest Surg 13, 253–260 (2009). https://doi.org/10.1007/s11605-008-0689-2
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DOI: https://doi.org/10.1007/s11605-008-0689-2