Open AccessNotch1 activation promotes renal cell carcinoma growth via PI 3 K / A kt signaling
Author(s) -
Xu Le,
Zhu Yu,
Xu Jiejie,
Wu Kerong,
Li Jinfeng,
Xu Wenping,
Liu Haiou,
Wang Shanshan,
Yin Hankun,
Chen Lin,
Wang Guomin,
Lin Zongming
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02291.x
Subject(s) - pi3k/akt/mtor pathway , clear cell renal cell carcinoma , protein kinase b , cancer research , cell growth , carcinogenesis , cell cycle , signal transduction , biology , microbiology and biotechnology , cell , chemistry , renal cell carcinoma , medicine , pathology , cancer , biochemistry , genetics
Both the N otch1 and PI 3 K /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 N otch1 signaling activity exerts its growth‐promoting effects via the PI 3K/ A kt 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 A kt (p A kt) 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 N otch1 signaling was activated in CCRCC tissue samples and cell lines. Notch1 activation increased CCRCC cell proliferation, enhanced anchorage‐independent growth, and accelerated G 1/S cell cycle progression. Such effects of the N otch1 signaling were, at least in part, mediated by the PI 3K/ A kt pathway. Correlations between N otch1, pA kt and K i‐67 protein levels in tissue microarrays reinforced our in vitro findings. Taken together, the current study established a functional link between the N otch1 and PI 3K/ A kt pathways in CCRCC . ( Cancer Sci 2012; 103: 1253–1258)