Claudia Nieva - Academia.edu (original) (raw)

Papers by Claudia Nieva

Trabajo presentado en el 17th International Ecdysone Workshop, celebrado en Ulm (Alemania) del 20... more Trabajo presentado en el 17th International Ecdysone Workshop, celebrado en Ulm (Alemania) del 20 al 24 de junio de 2008.

Proceedings of SPIE, Jun 1, 2012

It has been described that benign MCF10A breast cancer cell line suffers phenotypic changes towar... more It has been described that benign MCF10A breast cancer cell line suffers phenotypic changes toward malignancy when are cultured in sparse conditions. Using Raman spectroscopy with an InVia Raman microscope (Renishaw) with a backscattered configuration, we have studied the metabolic changes of confluent and sparse MCF10A cell cultures. We used Principal Component Analysis and Partial Least Squares Discriminant Analyses to assess the different profiling of the metabolic composition of breast cancer cells. The results indicated that Raman spectroscopy together with multivariate analysis is a useful technique to distinguish metabolic changes in malignant transformation. The identification of new metabolites, implementing the catalogue on the characterization of the different phenotypes associated to cell malignancy using Raman spectroscopy is under study.

ABSTRACT *The two authors contributed equally to this paper. **Corresponding author. Abstract—The... more ABSTRACT *The two authors contributed equally to this paper. **Corresponding author. Abstract—The identification of biomarkers in the primary tumor is essential for the stratification of breast cancer patients according to the risk of metastasis progression. To characterize the lipogenic phenotype of breast cancer metastatic cells, the Raman excitation was acquired using an InVia Raman microscope (Renishaw) with a backscattered configuration. The spectroscopic differences between metastatic variants, confirmed by Nile Red staining and fluorescence microscopy, indicate the biomedical application of Raman microspectroscopy to identify the metabolic phenotype of metastatic cells. Despite reduced mortality in breast cancer patients due to earlier diagnosis and implementation of adjuvant chemo- and hormone-therapies, breast cancer is still the most common cause of cancer death in women worldwide. Many factors and genes are involved in the initiation of breast cancer, but mortality is mainly due to metastatic disease. Like other cancer entities, breast cancer often shows organ preference in metastasis formation. Bone is the most common organ in which breast carcinomas establish distant metastases (60%). Moreover, lung (34 %) and liver (20%) are often colonized by metastatic carcinoma cells, although comparable therapeutic improvement is not always achieved. Brain metastases occur in 10-15% of breast cancer patients with advanced disease (1). It has been found that solid tumors may carry a specific gene expression signature mostly associated with metastasis and poor clinical outcome, suggesting that the metastatic potential of human tumors is encoded in the bulk of a primary tumor and that cells likely to metastasize are fundamentally different (2). We analyzed the differential expression of genes in brain metastasis in comparison to lung, bone and liver metastases, obtaining a list of organ-specific genes (3). One of the most interesting pathways we found is an over-expression of proteins related to synthesis of fatty acids in brain metastasis. Raman microspectroscopy, a technique based on the inelastic dispersion of monochromatic radiation, provides specific vibrational signatures of chemical bonds suitable for the analysis of saturated and unsaturated fatty acids (4). We used this technique to validate transcriptomic data and to characterize the lipogenic phenotype of breast cancer metastatic cells.

Archives of Insect Biochemistry and Physiology, 2007

The small G protein Ran, which is important for nucleocytoplasmic shuttling of proteins is presen... more The small G protein Ran, which is important for nucleocytoplasmic shuttling of proteins is present, but does not interact with EcR, Usp, and EcR/Usp. As shown by oligomycin treatment, EcR, Usp, and EcR/Usp import is energy dependent. Export of EcR and EcR/Usp is mediated by exportin‐1 (CRM‐1) as shown by the inhibiting effect of leptomycin B (LMB). Usp remains in the nucleus for more than 24 h. Nuclear retainment of EcR and Usp is energy dependent as shown by treatment with oligomycin. No export signal could be identified for Usp. The data confirm that EcR and Usp can enter the nucleus independently and that intracellular localization is regulated individually for each receptor. It is also demonstrated that the export signal of EcR is inaccessible after heterodimerization with Usp. Arch. Insect Biochem. Physiol. 65:134–142, 2007. © 2007 Wiley‐Liss, Inc.

Analytical Chemistry, Mar 28, 2018

Raman spectroscopy (RS) has shown promise as a tool to reveal biochemical changes that occur in c... more Raman spectroscopy (RS) has shown promise as a tool to reveal biochemical changes that occur in cancer processes at the cellular level. However, when analysing clinical samples, RS requires improvements to be able to resolve biological components from the spectra. We compared the strengths of Multivariate Curve Resolution (MCR) versus Principal Component Analysis (PCA) to deconvolve meaningful biological components, formed by distinct mixtures of biological molecules, from a set of mixed spectra. We exploited the flexibility of the MCR algorithm to easily accommodate different initial estimates and constraints. We demonstrate the ability of MCR to resolve undesired background signals from the RS that can be subtracted to obtain clearer cancer cell spectra. We used two triple negative breast cancer cell lines, MDA-MB 231 and MDA-MB 435, to illustrate the insights obtained by RS that infer the metabolic changes required for metastasis progression. Our results show that increased levels of amino acids and lower levels of mitochondrial signals are attributes of bone metastatic cells, whereas lung metastasis tropism is characterized by high lipid and mitochondria levels. Therefore, we propose a method based on the MCR algorithm to achieve unique biochemical insights into the molecular progression of cancer cells using RS.

Plant Molecular Biology, Aug 1, 2005

El artículo seleccionado no se encuentra disponible por ahora a texto completo por no haber sido ... more El artículo seleccionado no se encuentra disponible por ahora a texto completo por no haber sido facilitado todavía por el investigador a cargo del archivo del mismo.

Development, Mar 1, 2011

RTK/Ras/MAPK signaling pathways play key functions in metazoan development, but how they control ... more RTK/Ras/MAPK signaling pathways play key functions in metazoan development, but how they control expression of downstream genes is not well understood. In Drosophila, it is generally assumed that most transcriptional responses to RTK signal activation depend on binding of Ets-family proteins to specific cis-acting sites in target enhancers. Here, we show that several Drosophila RTK pathways control expression of downstream genes through common octameric elements that are binding sites for the HMGbox factor Capicua, a transcriptional repressor that is downregulated by RTK signaling in different contexts. We show that Torso RTK-dependent regulation of terminal gap gene expression in the early embryo critically depends on Capicua octameric sites, and that binding of Capicua to these sites is essential for recruitment of the Groucho co-repressor to the huckebein enhancer in vivo. We then show that subsequent activation of the EGFR RTK pathway in the neuroectodermal region of the embryo controls dorsal-ventral gene expression by downregulating the Capicua protein, and that this control also depends on Capicua octameric motifs. Thus, a similar mechanism of RTK regulation operates during subdivision of the anterior-posterior and dorsal-ventral embryonic axes. We also find that identical DNA octamers mediate Capicua-dependent regulation of another EGFR target in the developing wing. Remarkably, a simple combination of activator-binding sites and Capicua motifs is sufficient to establish complex patterns of gene expression in response to both Torso and EGFR activation in different tissues. We conclude that Capicua octamers are general response elements for RTK signaling in Drosophila.

PLOS ONE, 2012

<p>A) The gene expression of epithelial cell markers (E-cadherin, cytokeratin 18) and the m... more <p>A) The gene expression of epithelial cell markers (E-cadherin, cytokeratin 18) and the mesenchymal cell marker vimentin were examined by RT and real-time PCR using 200 ng of RNA. E-cadherin and CK18 are represented compared to the luminal MCF7 cell line expression and vimentin is represented compared to the MDA-MB-231 cell line. Cyclophilin A gene was used to normalize gene expression. B) Immunofluorescence staining of the epithelial E-cadherin and the mesenchymal vimentin markers in MCF7, MDA-MB-468, MCF10A, SKBR3, MDA-MB-231 and MDA-MB-435 cells. DAPI staining appears minimized in each picture. 40× magnification was used.</p

Oncogene, 2012

Little is known about metastatic pathways that are specific to the lung rather than other organs.... more Little is known about metastatic pathways that are specific to the lung rather than other organs. We previously showed that antioxidant proteins such as peroxiredoxins were specifically upregulated in lung metastatic breast cancer cells. We hypothesize that cancer cells that live under aerobic conditions, as might be the case in lungs, protect themselves against the damage caused by reactive oxygen species (ROS). To examine this hypothesis, we studied the role of peroxiredoxin-2 (PRDX2) in lung vs bone metastasis formation. A metastatic variant of MDA-MB-435 breast cancer cells that specifically metastasize to lungs (435-L3) was transduced with short hairpin RNAs to specifically silence PRDX2. Conversely, a bone metastatic variant of MDA-MB-231 cells (BO2) was stably transfected to overexpress PRDX2. The 435-L3 cells silenced for PRDX2 were significantly more sensitive to H 2 O 2-induced oxidative stress than the parental and scrambled transfected cells. BO2/PRDX2 cells produced less ROS than BO2/green fluorescent protein control cells under oxidative stress. Moreover, PRDX2 knockdown inhibited the growth of 435-L3 cells in the lungs, whereas lymph node metastasis remained unaffected. In contrast, PRDX2 overexpression in bone metastatic BO2 breast cancer cells led to drastic inhibition of the skeletal tumor burden and reduction of bone destruction. Furthermore, PRDX2 expression in breast cancer cells was associated with a glucose-dependent phenotype, different from bone metastatic cells. Overall, our results strongly suggest that PRDX2 is a targetable 'metabolic adaptor' driver protein implicated in the selective growth of metastatic cells in the lungs by protecting them against oxidative stress.

2011 International Workshop on Biophotonics, 2011

Postembryonic development of holometabolous and hemimetabolous insects occurs through successive ... more Postembryonic development of holometabolous and hemimetabolous insects occurs through successive molts triggered by 20-hydroxyecdysone (20E). The molecular action of 20E has been extensively studied in holometabolous insects, but data on hemimetabolous are scarce. We have demonstrated that during the nymphal development of the hemimetabolous insect Blattella germanica, 20E binds to the heterodimeric receptor formed by the nuclear receptors BgEcR-A and BgRXR activating a cascade of gene expression, including the nuclear receptors BgE75 and BgHR3. Herein, we report the characterization of BgFTZ-F1, another nuclear hormone receptor involved in 20E action. BgFTZ-F1 is activated at the end of each instar, and RNAi has demonstrated that BgHR3 is needed for BgFTZ-F1 activation, and that BgFTZ-F1 has critical functions of during the last nymphal instar. Nymphs with silenced BgFTZ-F1 cannot ecdyse, arrest development, and show structures of ectodermal origin duplicated. BgFTZ-F1 also control...

Trabajo presentado en la 9th International Conference on Juvenile Hormones, celebrada en York (UK... more Trabajo presentado en la 9th International Conference on Juvenile Hormones, celebrada en York (UK) del 5 al 10 de agosto de 2007.

Trabajo presentado en el Insect Hormones (19th Ecdysone) International Workshop, celebrado en Min... more Trabajo presentado en el Insect Hormones (19th Ecdysone) International Workshop, celebrado en Minneapolis del 21 al 26 de julio de 2013.