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    Proepithelin is an autocrine growth factor for bladder cancer

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    Morrione-JournalArticle-2009.pdf
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    Genre
    Journal article
    Date
    2009-02-23
    Author
    Lovat, Francesca
    Bitto, Alessandro
    Xu, Shi-Qiong
    Fassan, Matteo
    Goldoni, Silvia
    Metalli, David
    Wubah, Vera
    McCue, Peter
    Serrero, Ginette
    Gomella, Leonard G.
    Baffa, Raffaele
    Iozzo, Renato V.
    Morrione, Andrea cc
    Show allShow less
    Department
    Biology
    Subject
    Bladder cancer
    Growth factor
    Autocrin
    Grn gene
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/7102
    
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    DOI
    https://doi.org/10.1093/carcin/bgp050
    Abstract
    The growth factor proepithelin functions as an important regulator of proliferation and motility. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian and renal cancer, as well as glioblastomas. Using recombinant proepithelin on 5637 transitional cell carcinoma-derived cells, we have shown previously that proepithelin plays a critical role in bladder cancer by promoting motility of bladder cancer cells. In this study, we used the ONCOMINE database and gene microarray analysis tool to analyze proepithelin expression in several bladder cancer microarray studies. We found a statistically significant increase in proepithelin messenger RNA expression in bladder cancers vis-à-vis non-neoplastic tissues, and this was associated with pathologic and prognostic parameters. Targeted downregulation of proepithelin in T24 transitional carcinoma cells with small hairpin RNA inhibited both Akt and mitogen-activated protein kinase pathways, severely reduced the ability of T24 cells to proliferate in the absence of serum and inhibited migration, invasion and wound healing. In support of these in vitro results, we discovered that proepithelin expression was significantly upregulated in invasive bladder cancer tissues compared with normal urothelium. In addition, proepithelin was secreted in the urine, where it was detectable by immunoblotting and enzyme-linked immunosorbent assay. Collectively, these results support the hypothesis that proepithelin may play a critical role as an autocrine growth factor in the establishment and progression of bladder cancer and suggest that proepithelin may prove a novel biomarker for the diagnosis and prognosis of bladder neoplasms.
    Citation
    Francesca Lovat, Alessandro Bitto, Shi-Qiong Xu, Matteo Fassan, Silvia Goldoni, David Metalli, Vera Wubah, Peter McCue, Ginette Serrero, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo, Andrea Morrione, Proepithelin is an autocrine growth factor for bladder cancer, Carcinogenesis, Volume 30, Issue 5, May 2009, Pages 861–868, https://doi.org/10.1093/carcin/bgp050
    Citation to related work
    Oxford University Press
    Has part
    Carcinogenesis, Vol. 30, No. 5
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    ae974a485f413a2113503eed53cd6c53
    http://dx.doi.org/10.34944/dspace/7082
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