Nuestros investigadores

Teresa Ezponda Itoiz

Publicaciones científicas más recientes (desde 2010)

Autores: Ezponda, Teresa; Romero, Juan Pablo; et al.
ISSN 0390-6078  Vol. 104  2019  págs. 88 - 88
Autores: Ezponda, Teresa; Meydan, C.; et al.
ISSN 0390-6078  Vol. 104  2019  págs. 11 - 11
Autores: Martinez-Terroba, E.; Ezponda, Teresa; et al.
ISSN 0023-6837  Vol. 98  Nº 12  2018  págs. 1562 - 1574
In recent years, the relevance of RNA metabolism has been increasingly recognized in a variety of diseases. Modifications in the levels of RNA-binding proteins elicit changes in the expression of cancer-related genes. Here we evaluate whether SRSF1 regulates the expression of DNA repair genes, and whether this regulation has a relevant role in lung carcinogenesis. An in silico analysis was performed to evaluate the association between the expression of SRSF1 and DNA repair genes. In vitro functional analyses were conducted in SRSF1 or DNA ligase 1 (LIG1)-downregulated non-small cell lung cancer (NSCLC) cell lines. In addition, the prognostic value of LIG1 was evaluated in NSCLC patients by immunohistochemistry. We found a significant correlation between the DNA repair gene LIG1 and SRSF1 in NSCLC cell lines. Moreover, SRSF1 binds to LIG1 mRNA and regulates its expression by increasing its mRNA stability and enhancing its translation in an mTOR-dependent manner. Furthermore, siRNA-mediated LIG1 inhibition reduced proliferation and increased apoptosis of NSCLC cells. Finally, the expression of LIG1 was an independent prognostic factor for NSCLC, as confirmed in a series of 210 patients. These results show that LIG1 is regulated by the oncoprotein SRSF1 and plays a relevant role in lung cancer cell proliferation and progression. LIG1 is associated with poor prognosis in non-small lung cancer patients.
Autores: San José, Edurne; Ezponda, Teresa; et al.
ISSN 1949-2553  Vol. 9  Nº 16  2018  págs. 12842 - 12852
Long Non-Coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. Several lncRNAs are involved in cell proliferation and are deregulated in several human tumors. Few lncRNAs have been described to play a role in Acute Lymphoblastic Leukemia (ALL). In this study, we carried out a genome wide lncRNA expression profiling in ALL samples and peripheral blood samples obtained from healthy donors. We detected 43 lncRNAs that were aberrantly expressed in ALL. Interestingly, among them, linc-PINT showed a significant downregulation in T and B-ALL. Re-expression of linc-PINT in ALL cells induced inhibition of leukemic cell growth that was associated with apoptosis induction and cell cycle arrest in G2/M phase. linc-PINT induced the transcription of HMOX1 which reduced the viability of ALL cells. Intriguingly, we observed that treatment with anti-tumoral epigenetic drugs like LBH-589 (Panobinostat) and Curcumin induced the expression of linc-PINT and HMOX1 in ALL. These results indicate that the downregulation of linc-PINT plays a relevant role in the pathogenesis of ALL, and linc-PINT re-expression may be one of the mechanisms exerted by epigenetic drugs to reduce cell proliferation in ALL.
Autores: Dupere-Richer, D.; Li, J. P. ; Maji, S. ; et al.
Revista: BLOOD
ISSN 0006-4971  Vol. 132  Nº Supl. 1  2018 
Autores: Ordonez, R.; Kulis, M.; Russinol, N.; et al.
ISSN 0390-6078  Vol. 102  Nº Supl. 2  2017  págs. 104 - 105
Autores: Carrasco, A.; Ezponda, Teresa; Meydan, C.; et al.
ISSN 0390-6078  Vol. 102  Nº Supl. 4  2017  págs. 10
Autores: Kulis, M.; Russinol, N.; et al.
ISSN 0390-6078  Vol. 102  Nº Supl. 4  2017  págs. 11 - 12
Autores: Ezponda, Teresa; Meydan, C.; et al.
ISSN 0390-6078  Vol. 102  Nº Supl. 2  2017  págs. 502 - 502
Autores: Carrasco, A.; Ezponda, Teresa; Meydan, C.; et al.
Revista: BLOOD
ISSN 0006-4971  Vol. 128  Nº 22  2016 
Autores: Pajares, María Josefa; Agorreta, J; Larráyoz, Marta; et al.
Revista: Journal of Clinical Oncology
ISSN 0732-183X  Vol. 30  Nº 10  2012  págs. 1129 - 1136
Purpose: Antiangiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have yielded more modest clinical benefit to patients with non-small-cell lung cancer (NSCLC) than initially expected. Clinical data suggest a distinct biologic role of the VEGF pathway in the different histologic subtypes of lung cancer. To clarify the influence of histologic differentiation in the prognostic relevance of VEGF-mediated signaling in NSCLC, we performed a concomitant analysis of the expression of three key elements of the VEGF pathway in the earliest stages of the following two principal histologic subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Patients and Methods: We evaluated tumor cell expression of VEGF, VEGF receptor (VEGFR) 1, and VEGFR2 using automatic immunostaining in a series of 298 patients with early-stage NSCLC recruited as part of the multicenter European Early Lung Cancer Detection Group project. A score measuring the VEGF signaling pathway was calculated by adding the tumor cell expression value of VEGF and its two receptors. The results were validated in two additional independent cohorts of patients with NSCLC. Results: The combination of high VEGF, VEGFR1, and VEGFR2 protein expression was associated with lower risk of disease progression in early SCC (univariate analysis, P = .008; multivariate analysis, hazard ratio, 0.62; 95% CI, 0.42 to 0.92; P = .02). The results were validated in two independent patient cohorts, confirming the favorable prognostic value of high VEGF signaling score in early lung SCC. Conclusion: Our results clearly indicate that the combination of high expression of the three key elements in the VEGF pathway is associated with a good prognosis in patients with early SCC but not in patients with ADC.
Autores: Pio, R, (Autor de correspondencia); Pajares, María Josefa; Aibar, E.; et al.
ISSN 1471-2164  Vol. 11  2010  págs. 352
Background: Microarrays strategies, which allow for the characterization of thousands of alternative splice forms in a single test, can be applied to identify differential alternative splicing events. In this study, a novel splice array approach was developed, including the design of a high-density oligonucleotide array, a labeling procedure, and an algorithm to identify splice events. Results: The array consisted of exon probes and thermodynamically balanced junction probes. Suboptimal probes were tagged and considered in the final analysis. An unbiased labeling protocol was developed using random primers. The algorithm used to distinguish changes in expression from changes in splicing was calibrated using internal non-spliced control sequences. The performance of this splice array was validated with artificial constructs for CDC6, VEGF, and PCBP4 isoforms. The platform was then applied to the analysis of differential splice forms in lung cancer samples compared to matched normal lung tissue. Overexpression of splice isoforms was identified for genes encoding CEACAM1, FHL-1, MLPH, and SUSD2. None of these splicing isoforms had been previously associated with lung cancer. Conclusions: This methodology enables the detection of alternative splicing events in complex biological samples, providing a powerful tool to identify novel diagnostic and prognostic biomarkers for cancer and other pathologies.
Autores: Ezponda, Teresa; Pajares, María Josefa; Agorreta, J; et al.
Revista: Clinical cancer research
ISSN 1078-0432  Vol. 16  Nº 16  2010  págs. 4113 - 4125
PURPOSE: SF2/ASF is a splicing factor recently described as an oncoprotein. In the present work, we examined the role of SF2/ASF in human non-small cell lung cancer (NSCLC) and analyzed the molecular mechanisms involved in SF2/ASF-related carcinogenesis. EXPERIMENTAL DESIGN: SF2/ASF protein levels were analyzed in 81 NSCLC patients by immunohistochemistry. SF2/ASF downregulation cellular models were generated using small interfering RNAs, and the effects on proliferation and apoptosis were evaluated. Survivin and SF2/ASF expression in lung tumors was analyzed by Western blot and immunohistochemistry. Survival curves and log-rank test were used to identify the association between the expression of the proteins and time to progression. RESULTS: Overexpression of SF2/ASF was found in most human primary NSCLC tumors. In vitro downregulation of SF2/ASF induced apoptosis in NSCLC cell lines. This effect was associated with a reduction in the expression of survivin, an antiapoptotic protein widely upregulated in cancer. In fact, SF2/ASF specifically bound survivin mRNA and enhanced its translation, via a mammalian target of rapamycin complex 1 (mTORC1) pathway-dependent mechanism, through the phosphorylation and inactivation of the translational repressor 4E-BP1. Moreover, SF2/ASF promoted the stability of survivin mRNA. A strong correlation was observed between the expression of SF2/ASF and survivin in tumor biopsies from NSCLC patients, supporting the concept that survivin expression levels are controlled by SF2/ASF. Furthermore, combined expression of these proteins was associated with prognosis. CONCLUSION: This study provides novel data on the mTORC1- and survivin-dependent mechanisms of SF2/ASF-related carcinogenic