Person:
López Barahona, Mónica

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Mónica

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López Barahona

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Ciencias Experimenales

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Post-transcriptional induction of β1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors.
(European Journal of Endocrinology, 1996) López Barahona, Mónica; Iglesias, Teresa; García Higuera, Irene; Mayor, Federico; Zaballos, Ángel; Bernal, Juan; Muñoz, Alberto
Thyroid hormone (triiodothyronine; T3) has been shown to control the expression of β1 -adrenergic receptors (β1-AR) in cardiac myocytes, but not in C6 glioma cells. This cell specificity has been attributed to low expression of T3 receptors and high expression of the c-erbAα2 splice variant that interferes with the action of T3. To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) α1 gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TRα1, but not wild-type cells, were responsive to T3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3 had no effect on β1-AR gene expression in either set of cells. The β1-AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of β1-AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the β1-AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of β1-AR expression in C6 cells is also exerted at the translational level, because there was no correlation between mRNA and protein induction, as determined by radioligand binding studies. We conclude that lack of responsiveness of the β1-AR gene in C6 cells to T3 is not due to high expression of c-erbAα2 but to undefined cell-specific factors.
Clonación humana reproductiva y terapéutica.
(Cuadernos de bioética, 2000) López Barahona, Mónica
Activation of phosphatidylcholine-specific phospholipase C in cell growth and oncogene transformation.
(Biochemical Society Transactions, 1989) Moscat, Jorge; Cornet, María E.; Díaz Meco, María T.; Larrodera, Pilar; López Alanon, Dulce; López Barahona, Mónica
Phospholipase C-mediated hydrolysis of phosphatidlycholine is an important step in PDGF-stimulated DNA synthesis.
(Cell, 1990) Larrodera, Pilar; Cornet, María E.; Díaz Meco, María T.; Henrik Guddal, Per; Johansen, Terje; López Barahona, Mónica; Diaz-Laviada, Inés; Moscat, Jorge
Recent evidence suggests the involvement of phosphatidylcholine (PC) hydrolysis both in the control of normal cell growth and in transformation. We show here that the simple exogenous addition of Bacillus cereus PC-hydrolyzing phospholipase C (PC-PLC) is sufficient to elicit a potent mitogenic response in Swiss 3T3 fibroblasts by a mechanism that is independent of protein kinase C. Our results on the additivity and synergism between B. cereus PC-PLC, PDGF, and insulin in the mitogenic response indicate that this novel phospholipid degradative pathway may be important in the mitogenic signaling cascade activated by PDGF.
Retinoic acid posttranscriptionally up-regulates proteolipid protein gene expression in C6 glioma cells.
(Journal of Biological Chemistry, 1993) López Barahona, Mónica; Miñano, M.; Mira, E.; Iglesias, T.; Stunnenberg, H G; Rodríguez-Peña, A; Bernal, J.; Muñoz, A.
The proteolipid protein (PLP) gene codes for the major central nervous system myelin protein. We have studied the effects of different agents on the expression of the PLP gene in C6 glioma cells. Retinoic acid (RA), but not dexamethasone, estradiol, insulin, growth hormone, or vitamin D3, had a drastic effect, increasing 10-20-fold the level of PLP mRNA. Concomitantly, RA also induced the appearance of the corresponding immunoreactive protein. The increase in PLP RNA level showed a slow kinetics and was blocked by cycloheximide, suggesting a posttranscriptional regulation by RA. Nuclear run-on assays confirmed that the rate of PLP gene transcription was unchanged by RA. In contrast, we found that retinoic acid augmented PLP mRNA stability, causing a substantial increase in its half-life. RA action was independent of cell density, serum, or PDGF but was partially inhibited by bFGF. On the other hand, thyroid hormone caused a moderate increase in PLP mRNA levels in C6 cells but only when the low numbers of thyroid receptors in these cells were increased by retrovirally mediated expression of an exogenous c-erbA/TR alpha-1 gene. Our results indicate that RA specifically up-regulates PLP expression in glioma C6 cells at a posttranscriptional level by increasing PLP RNA half-life.
Doxazosin in prostate cancer
(2006-11) Arencibia, José Manuel; Bonnin, Ana; López Barahona, Mónica
The TC21 oncoprotein interacts with the Ral guanosine nucleotide dissociation factor.
(Oncogene, 1996) López Barahona, Mónica; Bustelo, Xose R; Barbacid, Mariano
TC21 is a highly oncogenic member of he Ras superfamily of small GTP binding proteins. We have used the yeast two hybrid system to identify proteins that interact with an oncogenic form of the TC2I protein. cDNA clones encoding the carboxy-terminal region of the RalGDS protein were isolated from human B-cell and HeLa cDNA libraries. RalGDS is an exchange factor that stimulates GDP dissociation from Ral, another member of the Ras superfamily of proteins. The interaction between RalGDS to TC21 is direct and appears to be mediated by the effector domain of TC21 and the carboxy-terminal region of RalGDS. Moreover, RalGDS only binds to TC21 in its active, GTP-loaded configuration. These results suggest that RalGDS might be an effector molecule for TC21 and may participate in cross-talking between Ral and TC2I signalling pathways.
Rac-1 dependent stimulation of the JNK/SAPK signaling pathway by Vav.
(Oncogene, 1996) Crespo, Piero; Bustelo, Xose R; Aaronson, David S; Coso, Ornar A; López Barahona, Mónica; Barbacid, Mariano; Gutkind, J Silvio
The protein product of the human vav oncogene, Vav exhibits a number of structural motifs suggestive of a role in signal transduction pathways, including a leucine-rich region, a plekstrin homology (PH) domain, a cysteine-rich domain, two SH3 regions, an SH2 domain, and a central Dbl homology (DH) domain. However, the transforming pathway(s) activated by Vav has not yet been elucidated. Interestingly, DH domains are frequently found in guanine nucleotide-exchange factors for small GTP-binding proteins of the Ras and Rho families, and it has been recently shown that, whereas Ras controls the activation of mitogen activated kinases (MAPKs), two members of the Rho family of small GTPases, Rac 1 and Cdc42, regulate activity of stress activated protein kinases (SAPKs), also termed c-jun N-terminal kinases (JNKs). The structural similarity between Vav and other guanine nucleotide exchange factors for small GTP-binding proteins, together with the recent identification of biochemical routes specific for members of the Ras and Rho family of GTPases, prompted us to explore whether MAPK or JNK are downstream components of the Vav signaling pathways. Using the COS-7 cell transient expression system, we have found that neither Vav nor the product of the vav proto-oncogene, proto-Vav, can enhance the enzymatic activity of a coexpressed, epitope tagged MAPK. On the other hand, we have observed that, whereas proto-Vav can slightly elevate JNK/SAPK activity, oncogenic Vav potently activates JNK/SAPK to an extent comparable to that elicited by two guanine-nucleotide exchange factors for Rho family members, Dbl and Ost. We also show that point mutations in conserved residues within the cysteine rich and DH domains of Vav both prevent its ability to activate JNK/SAPK and render Vav oncogenically inactive. In addition, we found that coexpression of the Rac-1 N17 dominant inhibitory mutant dramatically diminishes JNK/SAPK stimulation by Vav, as well as reduces the focus-forming ability of Vav in NIH3T3 murine fibroblasts. Taken together, these findings provide the first evidence that Rac-1 and JNK are integral components of the Vav signaling pathway.
Kinetic evidence of a rapid activation of phosphatidylcholine hydrolysis by Ki-ras oncogene. Possible involvement in late steps of the mitogenic cascade.
(Journal of Biological Chemistry, 1990) López Barahona, Mónica; Kaplan, P.; Cornet, M E; Díaz Meco, María T.; Larrodera, Pilar; Diaz-Laviada, I; Municio, A.; Moscat, Jorge
A novel phospholipase C specific for phosphatidylcholine has been shown to be activated by several agonists. Also, recent evidence suggests that transformation mediated by the ras oncogene possibly involves the activation of this novel phospholipid degradative pathway which would account for the increased diacylglycerol levels associated with transformation. Here we use a mutant of Ki-ras which is temperature-sensitive for transformation to investigate the kinetics of activation of the phosphodiesterase-mediated turnover of phosphatidylcholine. Upon shift to the permissive temperature, products of the activated phosphatidylcholine-specific phospholipase C were detected by 30 min and reached maximal levels by 1-2 h. These results suggest that the product of the ras oncogene rapidly activates the phosphodiesteratic hydrolysis of phosphatidylcholine. Furthermore, the fact that at least 4 h are required for serum to activate this phospholipase C strongly suggests that the ras oncogene product might be involved in late steps of the mitogenic signaling cascade.
Ten Reasons Why People With Down Syndrome are Protected From the Development of Most Solid Tumors - A Review.
(Frontiers in Genetics, 2021) Osuna Marco, Marta Pilar; López Barahona, Mónica; López Ibor, Blanca; Tejera, Águeda
People with Down syndrome have unique characteristics as a result of the presence of an extra chromosome 21. Regarding cancer, they present a unique pattern of tumors, which has not been fully explained to date. Globally, people with Down syndrome have a similar lifetime risk of developing cancer compared to the general population. However, they have a very increased risk of developing certain tumors (e.g., acute leukemia, germ cell tumors, testicular tumors and retinoblastoma) and, on the contrary, there are some other tumors which appear only exceptionally in this syndrome (e.g., breast cancer, prostate cancer, medulloblastoma, neuroblastoma and Wilms tumor). Various hypotheses have been developed to explain this situation. The genetic imbalance secondary to the presence of an extra chromosome 21 has molecular consequences at several levels, not only in chromosome 21 but also throughout the genome. In this review, we discuss the different proposed mechanisms that protect individuals with trisomy 21 from developing solid tumors: genetic dosage effect, tumor suppressor genes overexpression, disturbed metabolism, impaired neurogenesis and angiogenesis, increased apoptosis, immune system dysregulation, epigenetic aberrations and the effect of different microRNAs, among others. More research into the molecular pathways involved in this unique pattern of malignancies is still needed.