FKBP51 increases the tumour-promoter potential of TGF-beta(230 views visite) Romano S, D'Angelillo A, D'Arrigo P, Staibano S, Greco A, Brunetti A, Scalvenzi M, Bisogni R, Scala I, Romano M
Clinical And Translational Medicine, 2014 Jan 27; 3(1): 1-1.
Keywords Parole chiave: Not available. Non disponibili.
Affiliations Affiliazioni: *** IBB - CNR ***
References Riferimenti: Not available. Non disponibili.
FKBP51 increases the tumour-promoter potential of TGF-beta
BACKGROUND: FKBP51 (FKBP5 Official Symbol) is a large molecular weight component of the family of FK506 binding proteins (FKBP). In recent years, research studies from our laboratory highlighted functions for FKBP51 in the control of apoptosis and melanoma progression. FKBP51 expression correlated with the invasiveness and aggressiveness of melanoma. Since a role for TGF-beta in the enhanced tumorigenic potential of melanoma cells is widely described, we hypothesized a cooperative effect between FKBP51 and TGF-beta in melanoma progression. METHODS: SAN and A375 melanoma cell lines were utilized for this study. Balb/c IL2gamma NOD SCID served to assess the ability to colonize organs and metastasize of different cell lines, which was evaluated by in vivo imaging. Realtime PCR and western blot served for measurement of mRNA and protein expression, respectively. RESULTS: By comparing the metastatic potential of two melanoma cell lines, namely A375 and SAN, we confirmed that an increased capability to colonize murine organs was associated with increased levels of FKBP51. A375 melanoma cell line expressed FKBP51 mRNA levels 30-fold higher in comparison to the SAN mRNA level and appeared more aggressive than SAN melanoma cell line in an experimental metastasis model. In addition, A375 expressed, more abundantly than SAN, the TGF-beta and the pro angiogenic TGF-beta receptor type III (TbetaRIII) factors. FKBP51 silencing produced a reduction of TGF-beta and TbetaRIII gene expression in A375 cell line, in accordance with previous studies. We found that the inducing effect of TGF-beta on Sparc and Vimentin expression was impaired in condition of FKBP51 depletion, suggesting that FKBP51 is an important cofactor in the TGF-beta signal. Such a hypothesis was supported by co immunoprecipitation assays, showing that FKBP51 interacted with either Smad2,3 and p300. In normal melanocytes, FKBP51 potentiated the effect of TGF-beta on N-cadherin expression and conferred a mesenchymal-like morphology to such round-shaped cells. CONCLUSIONS: Overall, our findings show that FKBP51 enhances some pro oncogenic functions of TGF-beta, suggesting that FKBP51-overexpression may help melanoma to take advantage of the tumor promoting activities of the cytokine.
FKBP51 increases the tumour-promoter potential of TGF-beta
Ntziachristos V, Cuénod CA, Fournier L, Balvay D, Pradel C, Siauve N, Clement O, Jouannot E, Lucidarme O, Vecchio SD, Salvatore M, Law B, Tung C-H, Jain RK, Fukumura D, Munn LL, Brown EB, Schellenberger E, Montet X, Weissleder R, Clerck ND, Postnov A * Tumor Imaging(302 visite) Textbook Of In Vivo Imaging In Vertebrates (ISSN: 9780-4700), 2007 Jul 16; 1: 277-309. Impact Factor:1.148 DettagliEsporta in BibTeXEsporta in EndNote
Aloj L, Aurilio M, Rinaldi V, D'Ambrosio L, Tesauro D, Peitl PK, Maina T, Mansi R, Von Guggenberg E, Joosten L, Sosabowski JK, Breeman WA, De Blois E, Koelewijn S, Melis M, Waser B, Beetschen K, Reubi JC, De Jong M * The EEE project(390 visite) Proc Int Cosm Ray Conf Icrc Universidad Nacional Autonoma De Mexico, 2007; 5(HEPART2): 977-980. Impact Factor:0 DettagliEsporta in BibTeXEsporta in EndNote
145 Records (133 escludendo Abstract e Conferenze). Impact factor totale: 552.304 (513.428 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 498.046 (456.256 escludendo Abstract e Conferenze).
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