title: Notch1 activation promotes renal cell carcinoma growth via PI3K/Akt signaling.
abstract: Both the Notch1 and PI3K/Akt pathways are aberrantly activated in clear cell renal cell carcinoma (CCRCC) and involved in the tumorigenesis. The aim of this study was to test our hypothesis that elevated Notch1 signaling activity exerts its growth-promoting effects via the PI3K/Akt pathway in CCRCC. To investigate the relationship between the two pathways, we enhanced and suppressed the Notch1 activity respectively in a CCRCC cell line through diverse means, and then evaluated ensuing phosphorylated Akt (pAkt) levels. To further study their collaboration in promoting tumor growth, cell proliferation assay, colony formation assay and cell cycle analysis were conducted under several different conditions. Immunostaining of the tissue microarrays was used to determine whether the phenomena we observed also existed in vivo. The results showed that Notch1 signaling was activated in CCRCC tissue samples and cell lines. Notch1 activation increased CCRCC cell proliferation, enhanced anchorage-independent growth, and accelerated G1/S cell cycle progression. Such effects of the Notch1 signaling were, at least in part, mediated by the PI3K/Akt pathway. Correlations between Notch1, pAkt and Ki-67 protein levels in tissue microarrays reinforced our in vitro findings. Taken together, the current study established a functional link between the Notch1 and PI3K/Akt pathways in CCRCC.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.forename: Kerong
authors.initials: K
authors.lastname: Wu
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.forename: Wenping
authors.initials: W
authors.lastname: Xu
authors.forename: Haiou
authors.initials: H
authors.lastname: Liu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.forename: Hankun
authors.initials: H
authors.lastname: Yin
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Guomin
authors.initials: G
authors.lastname: Wang
authors.forename: Zongming
authors.initials: Z
authors.lastname: Lin
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D046888:Tissue Array Analysis; D047368:Tumor Burden
chemical_list: D019394:Ki-67 Antigen; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt