Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recombinant plasmid pIJ3079 contains DNA sequences from Xanthomonas campestris pv campestris involved in coordinate negative regulation of production of the extracellular enzymes protease, endoglucanase, amylase and polygalacturonate lyase, and extracellular polysaccharide (EPS). Wild-type bacteria harbouring pIJ3079 and therefore carrying extra copies of the gene(s) therein showed reduced enzyme and EPS production and reduced aggressiveness to plants. Localised Tn5 mutagenesis of the corresponding region of the genome gave mutants producing higher levels of enzymes and EPS than the wild type, suggesting that the gene(s) may negatively regulate production in the normal cell. Enzyme and EPS production in the mutants was still dependent on previously characterised positive regulatory genes.
Mol Gen Genet 1990 Jun
PMID:Cloning of genes involved in negative regulation of production of extracellular enzymes and polysaccharide of Xanthomonas campestris pathovar campestris. 170 Feb 68

We found previously that transforming growth factor-beta 1 (TGF beta 1) mRNA levels are markedly elevated in rat prostate cancer (Dunning R3327 sublines) compared to levels in normal prostate. Our goal was to determine whether elevated expression of TGF beta 1 is biologically relevant to prostate cancer growth in vivo. We chose as our model the R3327-MATLyLu prostate cancer epithelial cell line, which produces metastatic anaplastic tumors when reinoculated in vivo. Our approach was to stably transfect MATLyLu cells with an expression vector that codes for latent TGF beta 1 and to isolate subclones of cells that over-expressed TGF beta 1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF beta 1 cDNA insert. We then studied the growth of these cells in vivo and in vitro. Twenty days after sc inoculation of 10(6) cells in vivo, TGF beta 1-overproducing MATLyLu tumors were 50% larger, markedly less necrotic, and produced more extensive metastatic disease (lung metastases in 73% of all lobes and lymph node metastases in 88% of animals) compared to control MATLyLu tumors (lung metastases, 21%; lymph node metastases, 7%). Thus, TGF beta 1 produced in vivo is biologically active and can promote prostate cancer growth, viability, and aggressiveness, perhaps via effects on the host and/or on the tumor cells themselves. When followed in vitro, TGF beta 1-overproducing cells became growth inhibited, but this effect was transient as cells subsequently resumed proliferating. Growth inhibition was due to TGF beta, because it could be prevented by TGF beta-neutralizing antibody. Therefore, prostate cancer cells can activate and respond to secreted latent TGF beta 1, and although the cells are transiently inhibited in vitro, there is no net inhibition of growth. The ability of the cells to respond to endogenously produced TGF beta 1 suggests that TGF beta 1 overexpression enhances tumor growth in vivo at least in part via an effect of TGF beta 1 on the tumor cells themselves.
Mol Endocrinol 1992 Jan
PMID:Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. 173 67

Histopathological examination of thymomas often fails to predict their malignant potential because the morphology of invasive or metastatic thymomas does not differ significantly from that of benign, encapsulated thymomas. In order to find a marker of aggressiveness in thymomas, 21 cases (9 non-invasive, 8 invasive and 4 metastatic thymomas) were examined for expression of the ras oncogene product p21 by immunohistochemistry and immunoblot analysis. Immunohistochemical study, using a serially diluted monoclonal antibody, NCC-RAS-001, demonstrated that neoplastic thymoma cells generally contained more p21 than normal thymic epithelial cells. Immunoblot analysis using another monoclonal antibody (NCC-RAS-004) also confirmed the increased concentration of p21 in all but one of the thymomas by comparison with normal thymic tissue. One metastatic thymoma did not have a band of p21 recognized by NCC-RAS-004 and was believed to have a deletion of the epitope recognized by this antibody. In addition, another metastatic thymoma showed abnormal electrophoretic mobility of p21. The increased amount of p21 in thymomas suggests that this protein has a role in the oncogenesis or progression of thymoma. The high incidence of a p21 molecular abnormality in metastatic thymomas indicates that the abnormality of this protein could be used as a possible marker of aggressive behavior.
Virchows Arch B Cell Pathol Incl Mol Pathol 1990
PMID:Expression of ras p21 protein by thymoma. 197 93

This interpretive review attempts to dovetail advanced work by different groups of investigators on blood group and carcinoma (CA) glycoconjugates that have terminal, immunoreactive Tn epitopes (GalNAc alpha-O-Ser/Thr), and on the interaction of those structures with complementary antibodies and lectins. Fenlon et al. (1987) and Leathem and Brooks (1987) found a positive correlation between primary breast CA aggressiveness and its affinity for Helix pomatia (HPA) lectin. This phenomenon was used successfully to accurately predict, in studies on 305 breast CA patients, early or late CA recurrence and patient survival time. The innate specificity of the large HPA combining groove (aside from its avid reactivity with appropriately spaced GalNAc alpha-O-) remains obscure, despite careful investigation for more than a decade (Baker et al., 1983). Leathem and Brooks presumed that HPA recognizes a hitherto "undefined biological marker" that indicates a breast CA's aggressiveness. Our own work has shown that the chemically fully defined Tn epitope, as measured with human polyclonal and murine monoclonal anti-Tn antibodies, occurs in immunoreactive form in approximately 90% of all breast and lung adenoCAs studied. Tn is occluded and non-reactive in healthy and non-CA-diseased tissues. We found that CA-associated Tn is an adhesion molecule in attachment to healthy cells; an increase in its density on breast CA cell membranes parallels greater aggressiveness of breast tumors in both humans and mice (the only species studied). Thus, Tn may be all or a major part of the postulated "as yet undefined biological marker" associated with high breast CA aggressiveness. Besides being helpful in the elucidation of some aspects of breast CA pathogenesis, these findings on primary breast CA have clinical implications in that they should facilitate stratification of breast CA patients for adjuvant treatment.
Mol Immunol 1989 Jan
PMID:Tn epitope (N-acetyl-D-galactosamine alpha-O-serine/threonine) density in primary breast carcinoma: a functional predictor of aggressiveness. 246 92

Immunohistochemical analysis of human cholesteatoma matrices revealed the presence of Langerhans' cells and T-lymphocytes. Through cell-to-cell interaction, Langerhans' cells probably play a key role in skin-related disorders, including cholesteatomas. They probably originate from a mobile cell population of monocyte origin and migrate into and out of the body's lining. Their custodial function is often carried out in close relation with T-lymphocytes. Monoclonal antibodies against Langerhans' cells and T-lymphocyte membrane receptors reveal the presence of these cell populations in cholesteatoma matrices but not in the tympanic membrane. Langerhans' cells and T-cell "traffic" through cholesteatomas are discussed in relation to the pathogenesis, natural course and recurrence of cholesteatomas. Through immunopathologic evaluation the clinical aggressiveness of a cholesteatoma may become predictable. It may even have consequences for the future handling of cholesteatomas.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Spatial distribution of Langerhans' cells and T-lymphocyte subpopulations in human tympanic membrane and aural cholesteatoma. 287 30

Genetic variation in a collection of 22 Pythium ultimum isolates was analyzed using restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNA (RAPD), and sequence characterized amplified regions (SCARs) as genetic markers. Qualitative evidence for the occurrence of sexual outcrossing in the field, asexual mechanisms affecting variation, and differences in aggressiveness between isolates was found. Codominant SCAR and RFLP markers detected multiple alleles in several isolates. Genetic analysis of F1 progeny from a cross indicates that heterozygosity is one cause of multiple alleles and contributes to genetic variation. Segregation analysis of F2 progeny fit diploid expectations and supported the use of the molecular markers for phenetic analysis. One isolate contained three alleles at one locus suggesting that polyploidy, aneuploidy or heterokaryosis may also contribute to genetic variation. Phenetic analysis using UPGMA clustering of Nei's distance calculated from RFLP data, UPGMA clustering of similarity matrixes calculated from RAPD data, and principle component analysis of RAPD data revealed no clustering of the three morphological types of Pythium ultimum (var. ultimum, var. sporangiferum, and group HS). Our results suggest that the three morphological variants of this homothallic oomycete are not genetically distinct.
Mol Plant Microbe Interact
PMID:Genetic variation in homothallic and hyphal swelling isolates of Pythium ultimum var. ultimum and P. utlimum var. sporangiferum. 787 81

GLUT3 glucose transporter gene expression is confined to neurons, while GLUT1 gene expression is limited to endothelial cells in normal brain. Thus far, neither of the GLUT genes has been shown to be consistently expressed in glial cells in adult brain in vivo under normal conditions. However, GLUT gene expression may be aberrant in human brain glial tumors. The present investigation shows that the GLUT1 and GLUT3 transcripts are differentially expressed in a series of 20 human brain tumors. The GLUT1/actin mRNA ratio increased in parallel to the astrocytoma grade, compared to a control human brain cortex, although no change in this ratio was seen in 5 meningiomas. Immunoreactive GLUT1 protein was not detectable in human brain tumors, including high-grade gliomas. Both 4.2 or 2.7 kb GLUT3/actin mRNA ratios showed a linear correlation with the glioma grade (P < 0.025), and the GLUT3-immunoreactive protein was also expressed in high grade gliomas. These studies provide evidence for induction of GLUT1 and GLUT3 gene expression in malignant glial cells, and the mRNA levels correlate with the biologic aggressiveness of the tumor. The detection of immunoreactive GLUT3, but not GLUT1, in the high grade gliomas suggest the GLUT3 isoform may be the predominant glucose transporter in highly malignant glial cells of human brain.
Brain Res Mol Brain Res 1994 Nov
PMID:Gene expression of GLUT3 and GLUT1 glucose transporters in human brain tumors. 787 54

The proto-oncogenes c-jun, junB, junD, and c-fos recently have been shown to encode for transcription factors with a leucine zipper that mediates dimerization to constitute active transcription factors; juns were shown to dimerize with each other and with c-fos, whereas fos was shown to dimerize only with juns. After birth, hematopoietic cells of the myeloid lineage, and some other terminally differentiated cell types, express high levels of c-fos. Still, the role of fos/jun transcription factors in normal myelopoiesis or in leukemogenesis has not been established. Recently, c-jun, junB, and junD were identified as myeloid differentiation primary response genes stably expressed following induction of terminal differentiation of myeloblastic leukemia M1 cells. Intriguingly, c-fos, though induced during normal myelopoiesis, was not induced upon M1 differentiation. To gain further insights into the role of fos/jun in normal myelopoiesis and leukemogenicity, M1fos and M1junB cell lines, which constitutively express c-fos and junB, respectively, were established. It was shown that enforced expression of c-fos, and to a lesser extent junB, in M1 cells results in both an increased propensity to differentiate and a reduction in the aggressiveness of the M1 leukemic phenotype. M1fos cells constitutively expressed immediate-early and late genetic markers of differentiated M1 cells. The in vitro differentiation of normal myeloblasts into mature macrophages and granulocytes, as well as the increased propensity of M1fos leukemic myeloblasts to be induced for terminal differentiation, was dramatically impaired with use of c-fos antisense oligomers in the culture media. Taken together, these observations show that the proto-oncogenes which encode for fos/jun transcription factors play important roles in promoting myeloid differentiation. The ability of the M1 leukemic myeloblasts to be induced for terminal differentiation in the absence of apparent fos expression indicates that there is some redundancy among the fos/jun family of transcription factors in promoting myeloid differentiation; however, juns alone cannot completely compensate for the lack of fos. Thus, genetic lesions affecting fos/jun expression may play a role in the development of "preleukemic" myelodysplastic syndromes and their further progression to leukemias.
Mol Cell Biol 1993 Feb
PMID:Proto-oncogenes of the fos/jun family of transcription factors are positive regulators of myeloid differentiation. 842 6

Cancer of the pancreas still has a very poor prognosis despite improved diagnostic methods and therapeutic regimens. The reasons for the aggressiveness of this cancer are not known, and the molecular mechanisms that govern the growth of pancreatic cancer cells are still not clearly defined. During the past two decades the development of new molecular biological techniques has offered new perspectives for a better understanding of pancreatic cancer. Tumor markers such as CA19-9 and CEA are used for diagnosis and for following the postoperative course of cancer patients. Characterization of pancreatic cancer cells using several molecular biological techniques has revealed overexpression or altered expression of growth factors and adhesion molecules, implying altered cell-cell and growth-regulatory interactions. In pancreatic cancer mutations in oncogenes and tumor suppressor genes are frequently detected in p53 and K-ras. This article reviews the possible molecular approaches for diagnosis, prognosis, or even therapy of pancreatic cancer.
J Mol Med (Berl) 1996 Jun
PMID:Molecular oncology in pancreatic cancer. 886 12

The serotonergic system controls the activity of neurotransmissions involved in numerous physiological functions. It is also thought to be crucially implicated in various pathologies, including psychiatric disorders such as depression, anxiety, and aggressiveness. The properties of 5-hydroxytryptamine (5-HT)-moduline, a novel endogenous peptide, have been tested in vitro and in vivo. Binding studies have shown that the peptide specifically interacts with 5-HT1B/1D receptors via a noncompetitive mechanism corresponding to a high apparent affinity (EC50 = 10(10) M). The interaction was shown in rat and guinea pig brain tissues and in cells transfected with either 5-HT1B or 5-HT1D beta receptor gene. [3H]5-HT-moduline binds to a single population of sites in mammalian brain (Kd = 0.4 nM in rat, Kd = 0.8 nM in guinea pig) as well as in transfected cells expressing the 5-HT1B or the 5-HT1D beta receptors (Kd = 0.2 and 0.6 nM, respectively). Furthermore, the binding is clearly specific of the LSAL sequence. Autoradiographic studies showed an heterogeneous brain distribution of this site. The interaction of 5-HT-moduline with the 5-HT1B/1D receptor corresponds to a decrease in the functional activity of the receptor (i.e., a decrease in the inhibitory effect of a 5-HT1B agonist on the evoked release of [3H]5-HT from synaptosomal preparation). It was also shown that 5-HT-moduline possess an in vivo effect in the social interaction test in mouse. Finally, it was demonstrated that 5-HT-moduline was released from brain synaptosomal preparation by a K+/Ca(2+)-dependent mechanism. In conclusion, 5-HT-moduline is a novel endogenous peptide regulating the serotonergic activity via a direct action at presynaptic 5-HT receptor. It may play an important role in the physiological mechanisms involving the serotonergic system, particularly in mechanisms corresponding to the elaboration of an appropriate response of the central nervous system to a given stimulus.
Mol Pharmacol 1996 Oct
PMID:5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors. 886 19


1 2 3 4 5 6 7 8 9 10 Next >>