Browsing by Author "Bernal, J."
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Item 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.Item Thyroid hormone regulates stromelysin expression, protease secretion and the morphogenetic potential of normal polarized mammary epithelial cells.(The EMBO Journal, 1995) López Barahona, Mónica; Fialka, I.; González Sancho, J. M.; Asunción, M.; González, M.; Iglesias, T.; Bernal, J.; Beug, H.; Muñoz, A.Stromelysins are a group of proteases which degrade the extracellular matrix and activate other secreted proteases. Stromelysin (ST)‐1 and ST‐2 genes are induced by tumor promoters, oncogenes and growth factors, and have been involved in acquisition of the malignant phenotype. We show here that the thyroid hormone (T3) increases ST‐1 and ST‐2 expression in a non‐transformed mouse mammary epithelial cell line (EpH4) in a way that is dependent on the level of thyroid receptor/c‐erbA (TR alpha‐1) expression. In agreement with this, T3 increases the secreted stromelysin activity and enhances the gelatinolytic activity of type IV collagenase. We have also demonstrated that T3 affects the epithelial polarity of EpH4 cells, diminishing the transepithelial electrical resistance of monolayers cultured on permeable filters, causing an abnormal distribution of polarization markers and the disruption of the organized 3‐D structures formed by these cells in type I collagen gels. These results indicate that the ligand‐activated TR alpha‐1 plays an important role in regulating the morphogenetic and invasive capacities of mammary epithelial cells. Because the c‐erbA locus is altered in several types of carcinoma, an altered or deregulated TR alpha‐1 expression may also be important for breast cancer development and metastasis.