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PubMed1979

Comparison of inducible and constitutive kynureninases of Neurospora crassa.

Two types of kynureninase were isolated from Neurospora crassa IFO 6068. The formation of one of them, which was separated from the inducible kynureninase by DEAE-cellulose chromatography, was independent of the presence of tryptophan in the growth medium. Ouchterlony double-diffusion analysis and immunochemical titration indicated that the constitutive-type enzyme is immunologically different from the inducible enzyme. We confirmed by a selective assay method with antiserum that the addition of tryptophan to the medium does not affect the formation of one of the enzymes (constitutive-type). The constitutive kynureninase was purified approximately 650-fold and was free of the inducible enzyme as judged by analytical gel electrophoresis. The molecular weight and optimum pH values of both enzymes are very similar. However, the constitutive enzyme shows much higher activity and affinity for L-3-hydroxykynurenine than for L-kynurenine, suggesting that the enzyme functions biosynthetically as a 3-hydroxykynureninase. Constitutive kynureninase activities were widely found in all the fungi tested, whereas the inducible enzyme activity was not present in Mucor or Rhizopus species. The inducible enzymes of all the Neurospora strains examined were shown to be immunologically identical.

Enzyme Induction↗
PubMed2005

[Consequences of the judgment of the Federal Constitutional Court on the fighting dog problem].

The Federal Constitutional Court decided with its "Dangerous dog-judgment" about the constitutional complaint of 53 dog breeders on the federal act combating dangerous dogs. This judgment was a so-called Pyrrhic Victory for the appellants. The Court declared the legislative competence of the federal level in this issue for null and void. But the statutory prohibition for breeding Pitbull-Terrier-, American Staffordshire-Terrier-, Staffordshire-Bullterrier-, Bullterrier-races and cross breeding out of this dogs will be governed in police laws by the Laender finally. The Standing Conference of the Ministers for Internal Affairs declared an appropriate recommendation. The use of the category "race" was refused by experts in discussions as completely wrong and not acceptable. But the Federal Constitutional Court reasons that the legislator can use the category "race" within his scope of evaluation and prognostication in accordance with the Constitution for the ban of import of dangerous dogs. The Court demands--because of the weak data background - that the legislator monitors the legislation, to adjust it according to current developments. The Constitutional Court creates with the judgment "dangerous dogs" legal certainty. The jurisprudence of the administrative courts of the Laender and of the Federal Administrative Court based on the category "race" was approved as well as the police laws of the Laender dealing with dangerous dogs.

Aggression↗
PubMed2005

Constitutive IL-8 expression in cancer cells is associated with mutation of p53.

We previously reported that most cancer cell lines constitutively express various cytokines including IL-8. But how IL-8 gene expression is regulated in cancer cells is still unclear. p53 tumor suppressor gene plays an important role in the regulation of transcription and is mutated in cancer cell lines. We investigated whether p53 status affects the constitutive expression of IL-8 in human cancer cells. SUIT-2 and RERF-LCOK cancer cells constitutively produced high levels of IL-8 in culture medium. Both cell lines were shown to carry a p53 mutation, and constitutive NF-kappaB transcriptional activity. To analyze whether p53 status mediates IL-8 expression, the effect of wild-type p53 (wt-p53) gene transfer on activation of NF-kappaB was determined in both cell lines. ELISA showed that the IL-8 concentration in medium decreased dose dependently by transient expression of wt-p53. Western-blot analysis showed no marked change in NF-kappaB protein levels in cell nuclei. EMSA showed no repression of NF-kappaB binding activity after transient expression of wt-p53. In contrast, luciferase reporter studies indicated that transcriptional activity of NF-kappaB is suppressed by transfection of wt-p53. These results show that wt-p53 gene transfer inhibits IL-8 production and NF-kappaB transcription activity in cancer cells and suggest that constitutive IL-8 production in cancer cells is associated with mutation of p53.

Cell Line, Tumor↗
PubMed2005

On Eulerian constitutive equations for modeling growth and residual stresses in arteries.

Recently Volokh and Lev (2005) argued that residual stresses could appear in growing arteries because of the arterial anisotropy. This conclusion emerged from a continuum mechanics theory of growth of soft biological tissues proposed by the authors. This theory included Lagrangian constitutive equations, which were formulated directly with respect to the reference configuration. Alternatively, it is possible to formulate Eulerian constitutive equations with respect to the current configuration and to 'pull them back' to the reference configuration. Such possibility is examined in the present work. The Eulerian formulation of the constitutive equations is used for a study of arterial growth. It is shown, particularly, that bending resultants are developed in the ring cross-section of the artery. These resultants may cause the ring opening or closing after cutting the artery in vitro as it is observed in experiments. It is remarkable that the results of the present study, based on the Eulerian constitutive equations, are very similar to the results of Volokh and Lev (2005), based on the Lagrangian constitutive equations. This strengthens the authors' argument that anisotropy is a possible reason for accumulation of residual stresses in arteries. This argument appears to be invariant with respect to the mathematical description.

Arteries↗
PubMed2006

Constitutive histone H2AX phosphorylation on Ser-139 in cells untreated by genotoxic agents is cell-cycle phase specific and attenuated by scavenging reactive oxygen species.

DNA damage, particularly when it involves formation of double-strand breaks (DSBs), triggers phosphorylation of histone H2AX on Ser-139. Phosphorylated H2AX has been named gammaH2AX, and induction of gammaH2AX in cells exposed to genotoxic agents is considered a sensitive and specific reporter of DNA damage. However, in untreated normal cells as well in the cells of various tumor lines cells, a fraction of histone H2AX molecules remain phosphorylated. In the present study, we observed that the extent of this constitutive H2AX phosphorylation varies depending on the cell type (line) and on cell cycle phase and, in most cell types, S and G(2)/M phase cells exhibit greater levels of H2AX phosphorylation than do cells in the G(1) phase. Furthermore, constitutive H2AX phosphorylation in human pulmonary carcinoma A549, lymphoblastoid TK6, and in normal bronchial epithelial cells was reduced following cell exposure to N-acetyl-L-cysteine, a scavenger of reactive oxygen intermediates; the reduction was most pronounced for G(2)M cells. Growth of A549 cells in the presence of buthionine sulfoximine, an inhibitor of glutathione synthetase, amplified the level of constitutive H2AX phosphorylation in A549 cells. The observed constitutive H2AX phosphorylation may be a reflection of the ongoing DNA damage mediated by reactive oxygen species (ROS) generated by metabolic activity during progression through the cell cycle, leading to formation of DSBs during the S phase. Because cumulative DNA damage in proliferating cells mediated by ROS is considered the key mechanism for cell ageing, the present approach to estimate the degree of attenuation of constitutive H2AX phosphorylation by antioxidants may provide a convenient tool to assess the DNA-protective and possible anti-ageing properties of other agents.

Antineoplastic Agents↗
PubMedDate not supplied

[Pharmacologic treatment of constitutional short stature].

The term constitutional short stature is used to describe clinical situations characterized by low stature, assessed using special growth nomograms, but which are not due to specific endocrine alterations, nor to genetic causes or skeletal dysmorphisms, nor secondary to specific organ pathologies or chronic diseases. On the basis of this definition, our paper also includes the so-called normal variants of short stature (familial short stature and constitutional delay of growth) and intrauterine growth retardation. The endocrine and auxological features of constitutional short stature are described in the literature and provide an adequate basis for the use of therapies which include, in addition to growth hormone, substances capable of stimulating the endogenous secretion of the hormone (L-dopa, bromocriptine, clonidine, GHRH, pyridostigmine), or anabolic hormones. Biosynthetic growth hormone therapy is without doubt the most widely used, both on account of the extensive clinical experience and due to the easy availability of the drug made possible by the use of the biosynthetic molecule. Many subjects affected by constitutional short stature show a good response to hGH therapy, whereas others do not benefit by this treatment. New therapies using GHRH and neurodrugs, which are certainly easier to handle and less expensive, represent a new approach to the therapy of constitutional short stature but this condition still requires further investigation.

Dwarfism↗
PubMed1989

[Selection of constitutive mutants of gram-positive cocci inducible resistant to macrolides, lincosamides and streptogramins (MLS): comparison of the selective effects of the MLS].

Mutation frequencies to constitutive resistance were determined for 7 strains inducible resistant to the MLS antibiotics (5 Staphylococcus aureus, 1 group G Streptococcus and 1 Streptococcus sanguis). In the 5 staphylococcal strains, mutants were generally selected at a frequency of 10(-9) to 10(-10) (ranging from 4.10(-8) to 9.10(-11) on plates containing 50 mg/l of the following non-inducer MLS: spiramycin, josamycin, midecamycin, miocamycin, lincomycin, clindamycin, and pristinamycin factor I (PI). No mutant was selected by 50 mg/l of pristinamycin factor II (PII) or by pristinamycin complex (P). Absence of selection of constitutive mutant by P was due to the low MICs of the antibiotic against the constitutively resistant strains and to the effect of PII: the emergence of the mutants constitutively resistant to PI was prevented by a 6-hour contact of the culture with PII (50 mg/l). MICs and MBCs of the pristinamycin against 9 constitutive mutants were respectively 2 to 4-fold and 2 to 8-fold greater than that against the wild-strains. In the streptococci, no constituvely resistant mutant was selected. Therefore, the risk of selection of resistant mutants by a non inducer MLS in the course of the treatment of infections due to inducible resistant staphylococcus appeared to be low, especially in the case of pristinamycin.

Aminoglycosides↗
PubMed1986

Constitutional delay in growth: comparison of linear growth with serum growth hormone response to provocative tests in 26 children.

The peak levels of serum growth hormone (GH) obtained in response to administration of insulin and arginine in 26 children with constitutional delay in growth (CDG) are compared to similar test results in 7 normal children. Heights at the time of testing, and follow-up linear growth, are documented in all subjects. Most patients with constitutional delay in growth could be identified on the basis of history, physical examination, bone age radiograph, and yearly follow-up of growth. Only two patients exhibited growth of less than 4 cm per year; both had normal responses to provocative testing. In response to provocative testing, individual patients with constitutional delay in growth revealed peak levels of serum GH which were within the normal range, but the group mean peak value was less (p less than 0.05) than in normal children. One child with clinical constitutional delay in growth revealed a subnormal response to both provocative tests. The results suggest that children with constitutional delay in growth may have a diminished reserve for secreting growth hormone.

Adolescent↗
PubMed1987

Constitutive expression of Slp genes in mouse strain B10.WR directed by C4 regulatory sequences.

The murine fourth component of complement (C4) and sex-limited protein (Slp) are two closely related serum proteins that exhibit very disparate patterns of gene expression: all mice constitutively express C4, whereas only adult male mice from a limited number of standard inbred strains express Slp. Several exceptional strains exhibit constitutive (C4-like) Slp expression, a phenotype that correlates with multiple copies of the Slp gene. To determine the molecular basis for constitutive Slp expression we have isolated genomic clones and compared the sequences of 1.5 kb of 5' flanking DNA from 1 C4 gene and three different Slp genes from the Slp-constitutive strain B10.WR. These sequence comparisons demonstrate C4-like regulatory sequences adjacent to two of the Slp genes. By analysis of cDNA clones isolated from a B10.WR liver library we demonstrate that the constitutive Slp phenotype is due primarily to expression of one of these C4/Slp hybrid genes. It appears likely that Slp gene duplication in strain B10.WR came about via homologous unequal crossover events between C4 and Slp genes; this would accommodate both the gene sequence data and the pattern of C4-like Slp expression in mouse strain B10.WR.

Animals↗
PubMed1995

Constitutively activating mutations of c-kit receptor tyrosine kinase confer factor-independent growth and tumorigenicity of factor-dependent hematopoietic cell lines.

The c-kit receptor tyrosine kinase (KIT) is activated upon ligand binding, thereby leading to a variety of signaling events that play a fundamental role in hematopoiesis. In addition to ligand-dependent activation, we have previously shown that KIT is constitutively activated in a ligand-independent manner by two point mutations, Val-559-->Gly (G559) mutation in the juxtamembrane domain and Asp-814-->Val (V814) mutation in the phosphotransferase domain. To investigate the biochemical consequence and biologic significance of these mutations, retroviral vectors encoding KITG559 or KITV814 were introduced into murine pro-B-type Ba/F3 cells and myeloid FDC-P1 cells, both of which require interleukin-3 (IL-3) for their growth and survival. In the cells, KITG559 or KITV814 were found to be constitutively phophorylated on tyrosine in the absence of stem cell factor (SCF) that is a ligand for KIT. Chemical cross-linking analysis showed that a substantial fraction of the phosphorylated KITG559 underwent dimerization even in the absence of SCF, whereas the phosphorylated KITV814 did not, suggesting the distinct mechanisms underlying constitutive activation of KIT by G559 and V814 mutations. Furthermore, the cells expressing either KITG559 or KITV814 were found to show a factor-independent growth, whereas the cells expressing wild-type KIT (KITWT) proliferated in response to SCF as well as IL-3. Moreover, subcutaneous injection of Ba/F3 cells expressing KITG559 or KITV814 into nude mice resulted in production of large tumors at all sites of the injection within 2 weeks, and all nude mice quickly succumbed to leukemia and died. These results suggest that, although the mechanisms underlying constitutive activation of KITG559 or KITV814 may be different, both of the activating mutations have a function to induce a factor-independent and tumorigenic phenotype. Also, the data of this study raise the possibility that the constitutively activating mutations of c-kit may play a causal role in development of hematologic malignancies.

Amino Acid Sequence↗
PubMed1995

Constitutive expression of human intercellular adhesion molecule-1 (ICAM-1) is regulated by differentially active enhancing and silencing elements.

While expression of intracellular adhesion molecule 1 (ICAM-1; CD54) is associated with chronic inflammation and autoimmune disease, and is also found on some tumours arising from ICAM-1-negative tissues, in apparently normal tissues it is restricted to a few cell types. Levels of constitutive ICAM-1 expression correlate with the levels of ICAM-1 mRNA. In order to identify regions of the gene regulating its constitutive expression, 5.8 kb of the 5' upstream region was studied in 16 human cell lines using transient transfection of reporter-gene constructs. Three enhancing and one silencing region were observed. While the enhancer upstream of position -1352 was active in all cells investigated, the inhibitory influence of a silencer region between positions -339 and -290 was observed only in 50% of the cells. All cells expressing low levels of ICAM-1, such as may occur in many tissues in vivo, lacked an active silencer. In contrast to the ICAM-1 low-expressing cells, cell lines with high constitutive ICAM-1 levels, as well as those with no ICAM-1 expression, showed an active silencer. Thus, ICAM-1 constitutive expression seems to be regulated in two different ways. The fact that silencer and enhancer activities were observed in both strongly positive and negative ICAM-1 cells, suggests that constitutive ICAM-1 expression is regulated by a balance of enhancing and silencing transcription factors and possible additional elements.

Base Sequence↗
PubMed1993

Heterologous processing of prosomatostatin in constitutive and regulated secretory pathways. Putative role of the endoproteases furin, PC1, and PC2.

Mammalian prosomatostatin (PSS) is cleaved at a dibasic Arg-Lys site to produce somatostatin-14 (SS-14) and at monobasic Arg and Lys sites to yield SS-28 and PSS(1-10) (antrin), respectively. Furin, PC1, and PC2 are three recently discovered mammalian endoproteases localized either to the constitutive (furin) or regulated (PC1, PC2) secretory pathways. In this study we have compared the heterologous processing of PSS in transiently transfected endocrine (AtT-20 pituitary) and nonendocrine (COS-7 monkey kidney, PC12 pheochromocytoma) tumor cells. We have correlated the efficiency of processing of PSS to SS-14, SS-28, and PSS(1-10) with (i) secretion through the constitutive or regulated pathways; (ii) endogenous expression of mRNA for furin, PC1, and PC2; and (iii) exogenous expression of PC1 and PC2 in cells that do not contain these enzymes in order to delineate the putative role of these enzymes in mediating PSS cleavage at dibasic and monobasic sites and to localize the proteolytic events to specific compartments of the secretory pathways. COS-7 and PC12 cells expressed only furin, secreted constitutively, and processed PSS preferentially at monobasic sites to SS-28 (40-43%) and antrin (27-29%). Processing, however, was inefficient as suggested by large amounts of unprocessed PSS. In contrast, AtT-20 cells showed regulated secretion, expressed all three endoproteases (with high levels of PC1), and processed PSS efficiently to mainly SS-14. PC1, but not PC2, exogenously coexpressed with PSS in COS-7 cells produced significant conversion to SS-14 but not SS-28. This study shows that PSS is capable of monobasic cleavage in the constitutive secretory pathway. Such processing could be mediated by a furin-like enzyme but is relatively inefficient. PC1 can effect dibasic cleavage of PSS whereas PC2 is without influence on PSS processing at least within the constitutive secretory pathway. Although monobasic and dibasic processing of PSS in COS-7 cells correlates with furin-like and PC1 activity, respectively, the relative inefficiency of such processing suggests that compartmentalization of proteolytic events in secretory vesicles or other more specific endoproteases may be required.

Animals↗
PubMed1997

Mechanisms of constitutive activation of c-kit receptor tyrosine kinase.

We investigated the mechanism of constitutive activation of c-kit receptor tyrosine kinase (KIT) found in the FMA3 murine mastocytoma cell line, and compared it with the mechanisms observed in other tumor mast cell lines (the HMC-1 human mast cell leukemia cell line, the RBL-2H3 rat mast cell leukemia cell line, and the P-815 murine mastocytoma cell line). The c-kit gene obtained from FMA3 cells was found to have 21-base deletion at the juxtamembrane domain of KIT, thereby leading to the constitutive activation of KIT. The deletion at the juxtamembrane domain resulted in constitutive dimerization of c-kit proteins, whereas the point mutation that were detected at the kinase domain of KIT in HMC-1, RBL-2H3, and P-815 cells caused constitutive activation of KIT without dimerization. These constitutively activating mutations of c-kit may play a role in development of mast cell tumors.

Animals↗
PubMed1998

A tyrosine-based signal present in Ig alpha mediates B cell receptor constitutive internalization.

B lymphocytes express Ag receptors (BCR) that are composed of ligand binding subunits, the membrane Igs, associated with Ig alpha/Ig beta heterodimers. One main BCR function is to bind and to internalize Ags. Peptides generated from these internalized Ags may be presented to T lymphocytes. Here, we have analyzed the involvement of BCR Ig alpha/Ig beta components in BCR constitutive endocytosis. The role of Ig alpha subunit in BCR constitutive endocytosis was first determined in the context of an IgM-based BCR. In contrast with BCR that contain wild-type Ig alpha, surface BCR lacking Ig alpha cytoplasmic domain were not constitutively internalized. The respective roles of Ig alpha and Ig beta subunits were then analyzed by expressing chimeric molecules containing the cytoplasmic domains of either subunits in a B cell line. Only the Ig alpha cytoplasmic domain contained an internalization signal that allowed constitutive endocytosis of Ig alpha chimeras via coated pits and accumulation in sorting-recycling endosomes. This internalization signal is contained in its immunoreceptor tyrosine-based activation motif. These results indicate that Ig alpha, through its immunoreceptor tyrosine-based activation motif, may account for the ability of IgM/IgD BCR to constitutively internalize monovalent Ags.

Amino Acid Sequence↗
PubMed1997

[Immunology in medical practice. V. Constitutional eczema].

Constitutional eczema (late atopic dermatitis) is a frequent condition: some 30% of the skin diseases seen by the GP involve constitutional eczema. A number of links with (external) factors have meanwhile been established. Patients with constitutional eczema often suffer from food allergy (over 60% of the children with the eczema) and many are allergic to airborne allergens (especially housedust mite allergen). The skin of patients with constitutional eczema has a diminished barrier function against irritants (soaps, acids, bases, water, detergents, biological juices (fruit, meat, fish, vegetables). In 90% of the patients with constitutional eczema the skin contains colonies of Staphylococcus aureus (in 5% of people without eczema). S. aureus can influence the eczema through exoantigens (so-called superantigens) and through conventional antigens that may evoke an IgE-mediated immune response. Emotional stress may influence the eczema. The close anatomical relationship between mast cells and nerve endings and between Langerhans cells and nerve endings suggest that the autonomous nervous system can modulate the immune system of the skin and consequently, the eczema. These factors should be taken into account in the treatment: reduction of exposure to food and airborne allergens and to irritants, treatment and prevention of S. aureus infections and psychological support. New therapies include cyclosporine, autologous IgG antigen complexes and phototherapy.

Adult↗
PubMed1998

Saturation mutagenesis of the beta subunit of the human granulocyte-macrophage colony-stimulating factor receptor shows clustering of constitutive mutations, activation of ERK MAP kinase and STAT pathways, and differential beta subunit tyrosine phosphorylation.

The high-affinity receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are heterodimeric complexes consisting of cytokine-specific alpha subunits and a common signal-transducing beta subunit (hbetac). We have previously demonstrated the oncogenic potential of this group of receptors by identifying constitutively activating point mutations in the extracellular and transmembrane domains of hbetac. We report here a comprehensive screen of the entire hbetac molecule that has led to the identification of additional constitutive point mutations by virtue of their ability to confer factor independence on murine FDC-P1 cells. These mutations were clustered exclusively in a central region of hbetac that encompasses the extracellular membrane-proximal domain, transmembrane domain, and membrane-proximal region of the cytoplasmic domain. Interestingly, most hbetac mutants exhibited cell type-specific constitutive activity, with only two transmembrane domain mutants able to confer factor independence on both murine FDC-P1 and BAF-B03 cells. Examination of the biochemical properties of these mutants in FDC-P1 cells indicated that MAP kinase (ERK1/2), STAT, and JAK2 signaling molecules were constitutively activated. In contrast, only some of the mutant beta subunits were constitutively tyrosine phosphorylated. Taken together, these results highlight key regions involved in hbetac activation, dissociate hbetac tyrosine phosphorylation from MAP kinase and STAT activation, and suggest the involvement of distinct mechanisms by which proliferative signals can be generated by hbetac.

Animals↗
PubMed1998

Beta1 integrin cytoplasmic domain regulates the constitutive conformation detected by MAb 15/7, but not the ligand-induced conformation.

The anti-integrin beta1 MAb 15/7 sometimes may be a reporter of integrin activation or ligand occupancy. However, certain beta1 tail deletions eliminate ligand binding despite inducing maximal constitutive 15/7 expression [Puzon-Mclaughlin et al. (1 996): J Biol Chem 271:16580-16585]. Here we describe beta1 tail mutations (e.g., double point mutations [D759L/F763L, F766L/E769L], or replacement of the beta1 tail by the beta5 tail) that prevent rather than induce constitutive appearance of the 15/7 epitope. Despite variable losses of constitutive 15/7 epitope, these mutants all retained a similar inducible 15/7 epitope component as seen upon incubation with GRGDSP peptide ligand. In addition, constitutive 15/7 expression did not correlate with integrin localization into focal adhesions. In conclusion, we show for the first time for a fully functional integrin that specific mutations within the beta1 tail can down-regulate the constitutive appearance of an extracellular conformation defined by MAb 15/7. Because this regulation occurs away from the ligand binding site and does not correlate with responsiveness to integrin ligand, cell adhesion, or localization into focal adhesions, a novel type of conformational regulation is suggested.

Amino Acid Sequence↗
PubMed1999

The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells.

Pancreatic adenocarcinoma is a leading cause of adult cancer mortality in the United States. Recent studies have revealed that point mutation of the K-ras oncogene is a common event in pancreatic cancer, and oncogenesis mediated by Ras may also involve activation of Rel/nuclear factor (NF)-kappa B transcription factors. Furthermore, the c-rel member of Rel/NF-kappa B transcription factor family was first identified as a cellular homologue of the v-rel oncogene, suggesting that other members of the Rel/NF-kappa B family are potentially oncogenes. We therefore investigated the possibility that Rel/NF-kappa B transcription factors are activated in pancreatic cancer. Immunohistochemical analysis, Western blot and Northern blot analysis, electrophoretic mobility shift assays, and chloramphenicol acetyltransferase assays were performed to determine RelA activity in human pancreatic adenocarcinomas and normal tissues and nontumorigenic or tumorigenic cell lines. RelA, the p65 subunit of NF-kappa B, was constitutively activated in approximately 67% (16 of 24) of pancreatic adenocarcinomas but not in normal pancreatic tissues. Constitutive RelA activity was also detected in 9 of 11 human pancreatic tumor cell lines but not in nontumorigenic Syrian golden hamster cell lines. I kappa B alpha, a previously identified NF-kappa B-inducible gene, was overexpressed in human pancreatic tumor tissues and cell lines, and RelA activation could be inhibited by curcumin and dominant-negative mutants of I kappa B alpha, raf, and MEKK1. This is the first report demonstrating constitutive activation of RelA in nonlymphoid human cancer. These data are consistent with the possibility that RelA is constitutively activated by the upstream signaling pathway involving Ras and mitogen-activated protein kinases in pancreatic tumor cells. Constitutive RelA activity may play a key role in pancreatic tumorigenesis through activation of its downstream target genes.

Adenocarcinoma↗