Expression and functional role of CRIPTO-1 in cutaneous melanoma.

Autor:	De Luca, A, Lamura, L, Strizzi, L, Roma, C, D'Antonio, A, Margaryan, N, Pirozzi, G, Hsu, M-Y, Botti, G, Mari, E, Hendrix, M J C, Salomon, D S, Normanno, N
Předmět:	MELANOMA FLOW cytometry IMMUNOHISTOCHEMISTRY CELL growth CARCINOGENESIS PROTEIN metabolism BENZAMIDE CANCER invasiveness CARRIER proteins CELL physiology CELL receptors CELL motility COMPARATIVE studies GLYCOPROTEINS GROWTH factors HETEROCYCLIC compounds IMMUNOENZYME technique RESEARCH methodology MEDICAL cooperation POLYMERASE chain reaction PROTEIN-tyrosine kinases PROTEINS RESEARCH RESEARCH funding RNA SKIN tumors TRANSFERASES WESTERN immunoblotting EVALUATION research REVERSE transcriptase polymerase chain reaction CANCER cell culture CHEMICAL inhibitors
Zdroj:	British Journal of Cancer; 9/27/2011, Vol. 105 Issue 7, p1030-1038, 9p, 1 Chart, 7 Graphs
Abstrakt:	Background: CRIPTO-1 (CR-1) is involved in the pathogenesis and progression of human carcinoma of different histological origin. In this study we addressed the expression and the functional role of CR-1 in cutaneous melanoma.Methods: Expression of CR-1 protein in melanomas and melanoma cell lines was assessed by immunohistochemistry, western blotting and/or flow cytometry. Levels of mRNA were evaluated by real-time PCR. Invasion assays were performed in Matrigel-coated modified Boyden chambers.Results: Expression of CR-1 protein and/or mRNA was found in 16 out of 37 primary human cutaneous melanomas and in 12 out of 21 melanoma cell lines. Recombinant CR-1 protein activated in melanoma cells c-Src and, at lesser extent, Smad signalling. In addition, CR-1 significantly increased the invasive ability of melanoma cells that was prevented by treatment with either the ALK4 inhibitor SB-431542 or the c-Src inhibitor saracatinib (AZD0530). Anti-CR-1 siRNAs produced a significant inhibition of the growth and the invasive ability of melanoma cells. Finally, a close correlation was found in melanoma cells between the levels of expression of CR-1 and the effects of saracatinib on cell growth.Conclusion: These data indicate that a significant fraction of cutaneous melanoma expresses CR-1 and that this growth factor is involved in the invasion and proliferation of melanoma cells. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu