Please use this identifier to cite or link to this item:
Title: Transcription factors Sp1 and p73 control the expression of the proapoptotic protein NOXA in the response of testicular embryonal carcinoma cells to cisplatin
Author: Grande, Lara
Bretones, Gabriel
Rosa-Garrido, Manuel
Garrido-Martin, Eva M.
Hernandez, Teresa
Fraile, Susana
Botella, Luisa M.
Alava, Enrique de
Vidal-Bel, August
García del Muro Solans, Xavier
Villanueva Garatachea, Alberto
Delgado, M. Dolores
Fernandez-Luna, Jose L.
Keywords: Apoptosi
Expressió gènica
Proteïnes supressores de tumors
Gene expression
Tumor suppressor protein
Issue Date: 3-Aug-2012
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: Testicular germ cell tumors (TGCTs) are highly responsive to and curable by cisplatin-based chemotherapy even in advanced stages. We have studied the molecular mechanisms involved in the induction of apoptosis in response to cisplatin, and found that proapoptotic Noxa is transcriptionally up-regulated following cisplatin exposure, even in the absence of p53, in NTERA2 cisplatin-sensitive cells but not in 1411HP-resistant cells. Blockade of Noxa reduced the apoptotic response of embryonal carcinoma (EC) NTERA2 cells to cisplatin. A detailed analysis of the Noxa promoter revealed that p73 and Sp1-like factors, Sp1 and KLF6, played key roles in the transcriptional control of this gene. Overexpression of TAp73 induced Noxa whereas the dominant negative isoform ΔNp73, reduced the levels of Noxa after cisplatin exposure in NTERA2 and 2102EP. Interestingly, down-regulation of Sp1 increased Noxa expression in response to cisplatin. However, blockade of KLF6 decreased cisplatin-induced up-regulation of Noxa in EC cell lines. In addition, tissue microarray analyses of TGCTs revealed that expression of Noxa correlates with good clinical prognosis in patients with embryonal carcinoma. Thus, our data show the transcriptional network that regulates Noxa in EC cells, which is key for their apoptotic response to cisplatin-based chemotherapy, and propose Noxa as a predictive factor of therapeutic response.
Note: Reproducció del document publicat a:
It is part of: Journal of Biological Chemistry, 2012, vol. 287, num. 32, p. 26495-26505
Related resource:
ISSN: 0021-9258
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
616694.pdf2.04 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.