English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/143142
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

Title

Spinophilin loss correlates with poor patient prognosis in advanced stages of colon carcinoma

AuthorsEstévez-García, Purificación; López-Calderero, Iker; Molina-Pinelo, Sonia; Muñoz-Galván, Sandra CSIC ORCID; Salinas, Ana; Gómez Izquierdo, Lourdes; Lucena-Cacace, Antonio; Felipe-Abrio, Blanca; Paz-Ares, Luis CSIC; García-Carbonero, Rocío CSIC ORCID; Carnero, Amancio CSIC ORCID
Issue DateJul-2013
PublisherAmerican Association for Cancer Research
CitationClinical Cancer Research 19(14): 3925-3935 (2013)
Abstract[Purpose+ The genomic region 17q21 is frequently associated with microsatellite instability and LOH in cancer, including gastric and colorectal carcinomas. This region contains several putative tumor suppressor genes, including Brca1, NM23, prohibitin, and spinophilin (Spn, PPP1R9B, neurabin II). The scaffold protein Spn is one of the regulatory subunits of phosphatase-1 (PP1) that targets PP1 to distinct subcellular locations and couples PP1 to its target. Thus, Spn may alter cell-cycle progression via the regulation of the phosphorylation status of the retinoblastoma protein, a direct target of PP1. Therefore, we analyzed whether Spn levels were reduced in colorectal carcinomas and whether Spn levels correlated with prognosis or response to therapy.
[Experimental Design] By means of immunohistochemistry or quantitative PCR, we studied the levels of Spn in stages II, III, and IV colorectal carcinoma tumors and correlated to other clinicopathologic features as well as prognosis or response to therapy.
[Results] Spn was lost in a percentage of human gastric, small intestine, and colorectal carcinomas. In patients with colorectal carcinoma, tumoral Spn downregulation correlated with a more aggressive histologic phenotype (poorer tumor differentiation and higher proliferative Ki67 index). Consistent with this observation, lower Spn protein expression levels were associated with faster relapse and poorer survival in patients with stage III colorectal carcinoma, particularly among those receiving adjuvant fluoropyrimidine therapy. We validated this result in an independent cohort of patients with metastatic colorectal carcinoma treated with standard chemotherapy. Although patients that achieved an objective tumor response exhibited Spn levels similar to nontumoral tissue, nonresponding patients showed a significant reduction in Spn mRNA levels.
[Conclusions] Our data suggest that Spn downregulation contributes to a more aggressive biologic behavior, induces chemoresistance, and is associated with a poorer survival in patients with advanced stages of colorectal carcinoma. © 2013 American Association for Cancer Research.
Publisher version (URL)http://doi.org/10.1158/1078-0432.CCR-13-0057
URIhttp://hdl.handle.net/10261/143142
DOIhttp://dx.doi.org/10.1158/1078-0432.CCR-13-0057
Identifiersissn: 1078-0432
e-issn: 1557-3265
Appears in Collections:(IBIS) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.