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Dive into the research topics where Nicolás P. Koritschoner is active.

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Featured researches published by Nicolás P. Koritschoner.


PLOS ONE | 2010

Nuclear Expression of KLF6 Tumor Suppressor Factor Is Highly Associated with Overexpression of ERBB2 Oncoprotein in Ductal Breast Carcinomas

Ricardo C. Gehrau; Diego S. D'Astolfo; Catherine I. Dumur; José Luis Bocco; Nicolás P. Koritschoner

Background Krüppel-like factor 6 (KLF6) is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes. Methodology/Principal Findings In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues in a microarray format representing fifteen human organs. Results indicate that while both nuclear and cytoplasmic distribution of KLF6 is detected in normal breast tissues, breast carcinomas express KLF6 mainly detected in the cytoplasm. Expression of KLF6 was further analyzed in breast cancer tissues overexpressing ERBB2 oncoprotein, which is associated with poor disease prognosis and patients survival. The analysis of 48 ductal carcinomas revealed a significant population expressing KLF6 predominantly in the nuclear compartment (X2 p = 0.005; Fisher p = 0.003). Moreover, this expression pattern correlates directly with early stage and small ductal breast tumors and linked to metastatic events in lymph nodes. Conclusions/Significance Data are consistent with a preferential localization of KLF6 in the nuclear compartment of early stage and small HER2-ERBB2 overexpressing ductal breast tumor cells, also presenting lymph node metastatic events. Thus, KLF6 tumor suppressor could represent a new molecular marker candidate for tumor prognosis and/or a potential target for therapy strategies.


Molecular Biology of the Cell | 2013

Rab1b overexpression modifies Golgi size and gene expression in HeLa cells and modulates the thyrotrophin response in thyroid cells in culture

Nahuel Romero; Catherine I. Dumur; Hernán Martinez; Iris A. García; Pablo Monetta; Ileana Slavin; Luciana Sampieri; Nicolás P. Koritschoner; Alexander A. Mironov; Maria Antonietta De Matteis; Cecilia Alvarez

An increase in Rab1b levels induces changes in Golgi size and in gene expression. These Rab1b-dependent changes require the activity of p38 mitogen-activated protein kinase and the cAMP-responsive element binding protein consensus binding. The results show a Rab1b increase in secretory cells after stimulation and suggest that this increase is required to elicit a secretory response.


Cell Death & Differentiation | 2008

Silencing of the transcription factor KLF6 by siRNA leads to cell cycle arrest and sensitizes cells to apoptosis induced by DNA damage

Diego S. D'Astolfo; Ricardo C. Gehrau; José Luis Bocco; Nicolás P. Koritschoner

Silencing of the transcription factor KLF6 by siRNA leads to cell cycle arrest and sensitizes cells to apoptosis induced by DNA damage


Biochemical Journal | 2000

Transcription of genes encoding pregnancy-specific glycoproteins is regulated by negative promoter-selective elements

Graciela M. Panzetta-Dutari; Nicolás P. Koritschoner; José Luis Bocco; Rodrigo Nores; Catherine I. Dumur; Luis C. Patrito

The human pregnancy-specific glycoprotein (PSG) genes comprise a family of 11 highly conserved members whose expression is maximal in placental cells and marginal in other cell types. We have investigated here the molecular basis of PSG regulation by analysing a large regulatory region of the PSG-5 gene in cells that do and do not express these genes. The promoter region (-254 to -43), which does not contain a TATA-box, large GC-rich sequences or a classical initiator, was active in all cell types analysed. Additional upstream sequences up to position -3204 repressed promoter activity. Two independent repressor regions were identified and found to operate effectively in HeLa, COS-7 and HTR8/SVneo placental cells. More significantly, these negatively acting modules failed to repress a heterologous TATA-containing thymidine kinase promoter. Detailed transcriptional and DNA-protein analyses of the proximal repressor region (-605 to -254) revealed the presence of both negative and positive cis-acting elements. Disruption of the repressive functions resulted in an enhanced transcription of the reporter constructs. In conclusion, these results demonstrate that PSG-5 gene transcription is highly repressed by promoter-selective negative regulatory regions and the relief of repression allows enhanced PSG-5 gene transcription irrespective of the cell type. Furthermore, our findings suggest that PSG genes are expressed mainly through a derepression mechanism.


Mutation Research | 2011

Differential expression of the klf6 tumor suppressor gene upon cell damaging treatments in cancer cells

Ricardo C. Gehrau; Diego S. D’Astolfo; Verónica Andreoli; José Luis Bocco; Nicolás P. Koritschoner

The mammalian Krüppel-like factor 6 (KLF6) is involved in critical roles such as growth-related signal transduction, cell proliferation and differentiation, development, apoptosis and angiogenesis. Also, KLF6 appears to be an emerging key factor during cancer development and progression. Its expression is thoroughly regulated by several cell-damaging stimuli. DNA damaging agents at lethal concentrations induce a p53-independent down-regulation of the klf6 gene. To investigate the impact of external stimuli on human klf6 gene expression, its mRNA level was analyzed using a cancer cell line profiling array system, consisting in an assortment of immobilized cDNAs from multiple cell lines treated with several cell-damaging agents at growth inhibitory concentrations (IC(50)). Cell-damaging agents affected the klf6 expression in 62% of the cDNA samples, though the expression pattern was not dependent on the cell origin type. Interestingly, significant differences (p<0.0001) in KLF6 mRNA levels were observed depending on the cellular p53 status upon cell damage. KLF6 expression was significantly increased in 63% of p53-deficient cells (122/195). Conversely, KLF6 mRNA level decreased nearly 4 fold in more than 70% of p53+/+ cells. In addition, klf6 gene promoter activity was down-regulated by DNA damaging agents in cells expressing the functional p53 protein whereas it was moderately increased in the absence of functional p53. Consistent results were obtained for the endogenous KLF6 protein level. Results indicate that human klf6 gene expression is responsive to external cell damage mediated by IC(50) concentrations of physical and chemical stimuli in a p53-dependent manner. Most of these agents are frequently used in cancer therapy. Induction of klf6 expression in the absence of functional p53 directly correlates with cell death triggered by these compounds, whereas it is down-regulated in p53+/+ cells. Hence, klf6 expression level could represent a valuable marker for the efficiency of cell death upon cancer treatment.


Journal of Biological Chemistry | 1997

A novel human zinc finger protein that interacts with the core promoter element of a TATA box-less gene.

Nicolás P. Koritschoner; José Luis Bocco; Graciela M. Panzetta-Dutari; Catherine I. Dumur; Alfredo Flury; Luis C. Patrito


Biology of Reproduction | 1999

The Krüppel-Like Core Promoter Binding Protein Gene Is Primarily Expressed in Placenta During Mouse Development

D. Slavin; Vincent Sapin; F. López-Díaz; P. Jacquemin; Nicolás P. Koritschoner; B. Dastugue; Irwin Davidson; Bruno Chatton; José Luis Bocco


FEBS Journal | 2004

Membrane distribution of epidermal growth factor receptors in cells expressing different gangliosides

Adolfo R. Zurita; Pilar M. Crespo; Nicolás P. Koritschoner; Jose L. Daniotti


Biochimica et Biophysica Acta | 2005

Genomic organization and functional analysis of the gene encoding the Krüppel-like transcription factor KLF6.

Ricardo C. Gehrau; Diego S. D'Astolfo; Claudio Prieto; José Luis Bocco; Nicolás P. Koritschoner


FEBS Journal | 1996

Analyses of Cis -Acting and Trans -Acting Elements that are Crucial to Sustain Pregnancy-Specific Glycoprotein Gene Expression in Different Cell Types

Nicolás P. Koritschoner; Graciela M. Panzetta‐Dutaiu; José Luis Bocco; Catherine I. Dumur; Alfredo Flury; Luis C. Patrito

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José Luis Bocco

National University of Cordoba

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Luis C. Patrito

National University of Cordoba

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Alfredo Flury

National University of Cordoba

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Catherine I. Dumur

National University of Cordoba

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Catherine I. Dumur

National University of Cordoba

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Diego S. D'Astolfo

National University of Cordoba

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Claudio Prieto

National University of Cordoba

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D. Slavin

National University of Cordoba

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