Notch1 expression correlates with tumor differentiation status in ovarian carcinoma
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Abstract
Notch signaling and its receptor Notch1 are expressed in ovarian epithelial tumors, but the relationship between Notch signaling and ovarian cancer remains to be elucidated. In this study, we detected the expression of Notch1 in ovarian tissues and human ovarian cancer cell lines. We also analyzed the expression of Notch1 and its relationship with differentiation status and FIGO (Federation International of Gynecology and Obstetrics) stage in ovarian cancer tissues. Immunohistochemistry, real-time polymerase chain reaction and Western blot were used to detect the expression of Notch1 in 109 ovarian cancer tissues, 65 patient-matched opposite side normal ovarian tissues and 48 normal ovarian tissues, together with A2780, HO-8910 and IOSE 144 cell lines. Our results showed that the expression of Notch1 in ovarian cancer tissues was higher than that in matched normal tissues and normal tissues, Notch1 is highly expressed in ovarian cancer cells A2780 and HO-8910. Moreover, expression of Notch1 increased gradually with the poor differentiating of cancer tissues and the increasing of FIGO stage in ovarian cancer tissues. It was concluded that Notch1 might be involved and play an oncogenic role in the development of ovarian cancer.
Keywords
Ovarian carcinoma Notch1 Notch signalingReferences
- 1.Paley PJ. Ovarian cancer screening: are we making any progress? Curr Opin Oncol. 2001;13(5):399–402.CrossRefPubMedGoogle Scholar
- 2.Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol. 2000;19(1):3–10.CrossRefPubMedGoogle Scholar
- 3.Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284(5415):770–6.CrossRefPubMedGoogle Scholar
- 4.Lai EC. Notch signaling: control of cell communication and cell fate. Development. 2004;131(5):965–73.CrossRefPubMedGoogle Scholar
- 5.Fortini ME. Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling. Nat Rev Mol Cell Biol. 2002;3(9):673–84.CrossRefPubMedGoogle Scholar
- 6.Kadesch T. Notch signaling: the demise of elegant simplicity. Curr Opin Genet Dev. 2004;14(5):506–12.CrossRefPubMedGoogle Scholar
- 7.Hansson EM, Lendahl U, Chapman G. Notch signaling in development and disease. Semin Cancer Biol. 2004;14(5):320–8.CrossRefPubMedGoogle Scholar
- 8.Axelson H. Notch signaling and cancer: emerging complexity. Semin Cancer Biol. 2004;14(5):317–9.CrossRefPubMedGoogle Scholar
- 9.Hopfer O, Zwahlen D, Fey MF, Aebi S. The Notch pathway in ovarian carcinomas and adenomas. Br J Cancer. 2005;93(6):709–18.CrossRefPubMedGoogle Scholar
- 10.Zagouras P, Stifani S, Blaumueller CM, et al. Alterations in Notch signaling in neoplastic lesions of the human cervix. Proc Natl Acad Sci USA. 1995;92(14):6414–8.CrossRefPubMedGoogle Scholar
- 11.Wang L, Qin H, Chen B, et al. Overexpressed active Notch1 induces cell growth arrest of HeLa cervical carcinoma cells. Int J Gynecol Cancer. 2007;17(6):1283–92.CrossRefPubMedGoogle Scholar
- 12.Miele L. Notch signaling. Clin Cancer Res. 2006;12(4):1074–9.CrossRefPubMedGoogle Scholar
- 13.Rose SL, Greenblatt D, Seiler N, Chen H. QS286. Notch 1 down-regulation by gamma-secretase inhibition decreases ovarian cancer cell growth. J Surg Res 2008;144(2):380.Google Scholar
- 14.Enomoto T, Weghorst CM, Inoue M, et al. K-ras activation occurs frequently in mucinous adenocarcinomas and rarely in other common epithelial tumors of the human ovary. Am J Pathol. 1991;139(4):777–85.PubMedGoogle Scholar
- 15.Tashiro H, Miyazaki K, Okamura H, et al. c-myc over-expression in human primary ovarian tumours: its relevance to tumour progression. Int J Cancer. 1992;50(5):828–33.CrossRefPubMedGoogle Scholar
- 16.Philp AJ, Campbell IG, Leet C, et al. The phosphatidylinositol 3′-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res. 2001;61(20):7426–9.PubMedGoogle Scholar
- 17.Yu H, Zhao X, Huang S, et al. Blocking Notch1 signaling by RNA interference can induce growth inhibition in HeLa cells. Int J Gynecol Cancer. 2007;17(2):511–6.CrossRefPubMedGoogle Scholar
- 18.Yao J, Qian C. Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3 K/Akt-dependent pathway. Med Oncol 2009.Google Scholar