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Mechanistic association of Notch 3 protein with the chemotherapy response of localized prostate cancer

American Journal of BioMedicine  Volume 2, Issue 8, pages 975-983, August 2014


Jones Lorenzoni; Lutz Hartsell; Johnstone Rades

Abstract

Prostate cancer is one of the most common cancers in American men. Genetics and age play a role in its development. Notch signaling pathway proteins are known to play critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thus it has been suggested that Notch may be responsible for the development and progression of human malignancies. The aim of this study is investigated the mechanistic role of Notch 3 with the chemotherapy response of patients with localized prostate cancer (PCa). A total of 772 patients with clinically localized PCa, confirmed by biopsy. Biochemical recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed with Kaplan-Meier curves. Various histopathological parameters were analyzed by univariate and multivariate analysis. Our results demonstrate that a high Notch 3 expression in prostate tumor represented a significantly higher possibility of being resistant to chemotherapy and reduced OS. Also, patients with high Notch 3 expression had a poorer prognosis than those with low Notch 3 expression. Further, in vitro studies showed that Notch 3 inhibition the proliferation, migration of invasiveness of prostate cancer. Consequently, we propose that Notch 3 protein is an important event that enhances tumor angiogenesis in human prostate cancer cells.

Keywords: Prostate cancer; Notch 3; multivariate analysis; chemotherapy


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