Abstract
Notch signaling controls cellular differentiation and proliferation. Recent studies have shown that Notch signaling plays an important role in the carcinogenesis and progression of a growing number of malignant tumors. We investigated the effect of Notch1 activation on human hepatocellular carcinoma (HCC). In five human HCC cell lines, it was found that SMMC7721 had relatively high while HepG2 relatively low expression of Notch1 and the activity of Notch signaling. Notch1 activation by transfection of active intracellular region of Notch1 (ICN1) into HCC HepG2 cells enhanced cell growth and proliferation, including invitro single cell colony formation, anchorage-independent proliferation, and invivo tumorigenicity. Notch1 activation also promoted HepG2 cell cycle progression. Suppression of Notch1 activation by RNAi of Notch1 or by γ-secretase inhibitor (GSI) in HCC SMMC7721 cells decreased cell growth capability and blocked cell cycle progression. Moreover, it was found that suppression of Notch1 activation induced SMMC7721 cell apoptosis, as demonstrated by apoptosis assays. These findings indicate that Notch1 activation promotes human HCC cell growth and proliferation, which may contribute to the progression of this type of malignant carcinoma.
Highlights
Notch signaling pathway is important for many types of cell fate determinations and essential for proper embryonic develop ment
We examined the expression of Notch1 in five human hepatocellular carcinoma (HCC) cell lines and found that SMMC7721 had the relatively high while HepG2 the relatively low expression of this molecule, and the active intracellular region of Notch1 (ICN1) was most abundant in SMMC7721 cells while undetectable in the other four cell lines [25]
We examined the activity of Notch signaling in these transfectants and found that Notch signaling was significantly inhibited by RNAi of Notch1 and was activated by transfection with ICN1 (Fig. 1B)
Summary
Notch signaling pathway is important for many types of cell fate determinations and essential for proper embryonic develop ment. Since Notch signaling affects cell differentiation, prolife ration and survival, recent studies have focused on its effects on malignant tumors and revealed its complex roles in cancer. Notch is identified as an oncogene responsible for acute T cell lymphoblastic leukemia (T-ALL) [4], and its oncogenic effects are found in glioma, primary melanoma and pancreatic cancer [5,6,7]. Notch contributes to the growth of human lung cancers by its effect on mitogen-activated protein kinase pathway [9]. Notch is found to correlate with Ki67, and GSI treatment arrests the growth of breast cancer cells [10]. In some circumstances, Notch is found to play a suppressive role. In human breast cancer, Notch expression decreases as tumor grade increases and Notch signaling suppresses tumor growth [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
