Biomedical subjects

A Kuo

Publications and source records attributed to A Kuo.

At least 73 records · Page 4Linked to original sources

PubMed1992

An embryonically expressed gene is a target for c-Myc regulation via the c-Myc-binding sequence.

We have used a subtraction/coexpression strategy involving two different tumors derived from c-myc-bearing transgenic mice to identify a gene that is a target for c-Myc regulation. The gene, expressed in certain embryonic and adult tissues and in several (but not all) c-myc-based tumors, bears a functional c-Myc-binding sequence located 3' to its transcription start site. This sequence is required for the binding of a nuclear protein complex which, by antibody analysis, includes c-Myc. This site is also required for expression of a reporter gene in chimeric constructs transfected into c-myc-overexpressing cells and, conversely, requires c-myc cotransfection for its enhanced expression in COS cells. Furthermore, transfection of c-myc blocks the normal down-regulation of this gene, which occurs in embryonic stem cells as they undergo differentiation. This target gene encodes an anonymous cDNA (ECA39) found previously to be amplified in a teratocarcinoma cell line.

Animals↗

PubMed1992

Cell density-dependent modulation of the Vibrio fischeri luminescence system in the absence of autoinducer and LuxR protein.

Expression of the Vibrio fischeri luminescence genes (luxR and luxICDABEG) in Escherichia coli requires autoinducer (N-3-oxohexanoyl homoserine lactone) and LuxR protein, which activate transcription of luxICDABEG (genes for autoinducer synthase and the luminescence enzymes), and cyclic AMP (cAMP) and cAMP receptor protein (CRP), which activate transcription of the divergently expressed luxR gene. In E. coli and in V. fischeri, the autoinducer-LuxR protein-dependent induction of luxICDABEG transcription (called autoinduction) is delayed by glucose, whereas it is promoted by iron restriction, but the mechanisms for these effects are not clear. To examine in V. fischeri control of lux gene expression by autoinducer, cAMP, glucose, and iron, lux::Mu dI(lacZ) and lux deletion mutants of V. fischeri were constructed by conjugation and gene replacement procedures. beta-Galactosidase synthesis in a luxC::lacZ mutant exhibited autoinduction. In a luxR::lacZ mutant, complementation by the luxR gene was necessary for luminescence, and addition of cAMP increased beta-galactosidase activity four- to sixfold. Furthermore, a luxI::lacZ mutant produced no detectable autoinducer but responded to its addition with induced synthesis of beta-galactosidase. These results confirm in V. fischeri key features of lux gene regulation derived from studies with E. coli. However, beta-galactosidase specific activity in the luxI::lacZ mutant, without added autoinducer, exhibited an eight- to tenfold decrease and rise back during growth, as did beta-galactosidase and luciferase specific activities in the luxR::lacZ mutant and luciferase specific activity in a delta(luxR luxICD) mutant. The presence of glucose delayed the rise back in beta-galactosidase and luciferase specific activities in these strains, whereas iron restriction promoted it. Thus, in addition to transcriptional control by autoinducer and LuxR protein, the V. fischeri lux system exhibits a cell density-dependent modulation of expression that does not require autoinducer, LuxR protein, or known lux regulatory sites. The response of autoinducer-LuxR protein-independent modulation to glucose and iron may account for how these environmental factors control lux gene expressions.

Cyclic AMP↗

PubMed1992

In situ hybridization reveals co-expression of embryonic and adult alpha globin genes in the earliest murine erythrocyte progenitors.

Murine erythropoiesis begins with the formation of primitive red blood cells in the blood islands of the embryonic yolk sac on day 7.5 of gestation. By analogy to human erythropoiesis, it has been thought that there is a gradual switch from the exclusive expression of the embryonic alpha-like globin (zeta) to the mature adult form (alpha) in these early mouse cells. We have used in situ hybridization to assess expression of these two globin genes during embryonic development. In contrast to what might have been expected, we find that there is simultaneous expression of both zeta and alpha genes from the very onset of erythropoiesis in the yolk sac. At no time could we detect expression of embryonic zeta globin mRNA without concomitant expression of adult alpha globin mRNA. Indeed, adult alpha transcripts exceed those of embryonic zeta in the earliest red cell precursors. Moreover, the pattern of hybridization reveals co-expression of both genes within the same cells. Even in the fetal liver, which supersedes the yolk sac as the major site of murine fetal erythropoiesis, there is a brief co-expression of zeta and alpha genes followed by the exclusive expression of the adult alpha genes. These data indicate an important difference in hematopoietic ontogeny between mouse and that of human, where zeta expression precedes that of alpha. In addition to resolving the embryonic expression of these globin genes, our results suggest that the embryonic alpha-like globin gene zeta may be physiologically redundant, even during the earliest stages of embryonic development.

Animals↗

PubMed1992

Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes.

The human T-cell leukemia virus type 1 (HTLV-I) is associated with adult CD4+ T-cell leukemia (ATL) and tropical spastic paraparesis (TSP). In as much as only a small percentage of individuals infected with HTLV-I develop either disease, we set out to model a genetic partner for this virus in an effort to understand and possibly reproduce its pathophysiology. To this end we have developed a binary set of transgenic mice, one bearing the relatively inactive HTLV-I long terminal repeat (LTR) positioned to drive the c-myc oncogene and another bearing a fusion transgene consisting of the immunoglobulin promoter/enhancer driving the gene for the HTLV-I transcription activator, tax. Alone, the tax construct, though expressed in the thymus, spleen, lung and brain, has no deleterious effect. Alone, the HTLV-I LTR/c-myc construct is expressed at very low levels in lymphoid cells and occasionally induces lymphomas in older animals. When these two transgenic lines are mated, bigenic offspring harboring both transgenes exhibit dramatic tumor formation. As in the human, these animals develop CD4+ T-cell lymphomas, but they also develop central nervous system tumors by 25-90 days of age. The syndrome, which is 100% penetrant and lethal, provides an animal model for adult T-cell lymphoma and a source of cultured cells of neurogenic origin.

Animals↗

PubMed1991

Detection of endothelial cell-reactive immunoglobulin in patients with anti-phospholipid antibodies.

Individuals with anti-phospholipid antibodies are at increased risk for the development of thrombosis and fetal loss. The pathogenesis of these syndromes is unknown, but may involve antibody-mediated alterations in endothelial cell coagulant activity. To address this possibility, we determined the incidence of endothelial cell-reactive antibodies in 76 patients whose plasma contained anti-phospholipid antibodies, but who had no clinically-evident immune disorder. Plasma from 47 patients deposited significantly more immunoglobulin on cultured endothelial cells than control plasma. Positive tests were more frequent in patients with a history of thrombosis than in those without (17/19 v 23/48; P = 0.004). However, we observed no correlation between immunoglobulin deposition on cardiolipin and endothelial cells by individual plasmas. Furthermore, endothelial cell reactivity was not diminished by adsorption of anti-cardiolipin antibodies from patient sera using liposomes. Immunoglobulin fractions prepared from 5/6 patient sera immunoprecipitated a approximately 70 kDa endothelial cell surface protein; 4/5 of these fractions also induced the release of von Willebrand factor from endothelial cells. These results demonstrate that plasma from many patients with anti-phospholipid antibodies, but no clinically-evident autoimmune disease, also contains endothelial cell-reactive antibodies. Detection of such antibodies might help identify individuals in this patient population at greatest risk for thrombosis.

Antibodies↗

PubMed1991

Effects of in utero ethanol exposure on the developing serotonergic system.

Previous work in this laboratory demonstrated that the 19- and 35-day-old offspring of ethanol-fed rats have a significant deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as a decrease in the number of total 5-HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5-HT and 5-HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5-HT1A receptors in the motor and somatosensory cortices contributes to the deficit of total 5-HT1 receptors. In contrast, we did not observe any changes in the binding to 5-HT1B receptors in these cortical regions from the 19-day-old offspring of ethanol-fed rats. The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5-HT and/or 5-HIAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5-HT1A receptors in the brain stem and in the acquisition of cortical 5-HT1A receptors. No changes were found in the binding of [125I]cyanopindolol to 5-HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Mechanisms of oncogene cooperation: activation and inactivation of a growth antagonist.

Gene transfer experiments have defined limitations with regard to the ability of individual oncogenes to transform cultured cells to a tumorigenic state. The stable transformation of REF52 cells by either the ras or sis oncogenes requires the continuous expression of a second collaborating oncogene, such as adenovirus-5 E1A or SV40 large T-antigen. Our studies suggest that the function of the nuclear collaborators is to antagonize dominant growth controls which limit the ability of REF52 cells to proliferate in response to mitogenic stimuli.

Adenovirus Early Proteins↗

PubMed1990

Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA.

Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC lead to an increase in its apparent molecular mass by approximately 40 Kd. The predominant u-PA binding protein isolated from whole cell detergent extracts migrated with a molecular mass of approximately 36 Kd using affinity chromatography. In contrast, when only cell surface proteins were radiolabeled before extraction, the predominant labeled u-PA binding protein isolated migrated with a molecular mass of approximately 46 Kd. Several pieces of evidence suggested that the difference in molecular mass between these two u-PA binding proteins resulted from glycosylation of a single receptor protein. First, a polyclonal antibody against u-PA receptor isolated from phorbol myristate acetate (PMA) stimulated U-937 cells reacted with both the 36- and 46-Kd proteins on Western blotting. Second, the size of the unmodified receptor was estimated by amplifying a full-length cDNA for u-PA receptor from an endothelial cell cDNA library using the polymerase chain reaction (PCR) and oligonucleotide primers corresponding to the DNA sequence of the receptor cloned from transformed human fibroblasts (Roldan et al, EMBO J 9:467, 1990). The size of the cDNA (approximately 1,054 base pairs, bp) and the presence of a single 1.4-kilobase (Kb) mRNA transcript on Northern blot analysis predict an unglycosylated receptor protein of approximately 35 Kd. Third, synthesis of 35S-labeled 46-Kd cell surface receptor protein was inhibited when the cells were grown in the presence of tunicamycin, while the synthesis of the 36-Kd species was unaffected. Moreover, the apparent molecular mass of purified surface-labeled receptor (approximately 46 Kd) was reduced by N-glycanase. These studies suggest that the u-PA receptor on the surface of HUVEC is a glycoprotein derived from a protein of approximately 35 Kd which is similar immunologically to u-PA receptors on other cell types.

Base Sequence↗

PubMed1990

Interaction of single-chain urokinase-type plasminogen activator with human endothelial cells.

The interaction of urokinase-type plasminogen activators with receptors on the surface of endothelial cells may play an important role in the regulation of fibrinolysis and cell migration. Therefore, we investigated whether human umbilical vein endothelial cells (HUVEC) express receptors for single-chain urokinase (scu-PA) on the cell surface and examined the effect of such binding on plasminogen activator activity. Binding of 125I-labeled scu-PA to HUVEC, performed at 4 degrees C, was saturable, reversible, and specific (k+1 4 +/- 1 X 10(6) min-1 M-1, k-1 6.2 +/- 1.4 X 10(-3) min-1, Kd 2.8 +/- 0.1 nM; Bmax 2.2 +/- 0.1 X 10(5) sites/cell; mean +/- S.E.). Binding of radiolabeled scu-PA was inhibited by both natural and recombinant wild-type scu-PA, high molecular weight two-chain u-PA (tcu-PA), catalytic site-inactivated tcu-PA, an amino-terminal fragment of u-PA (amino acids 1-143), and a smaller peptide (amino acids 4-42) corresponding primarily to the epidermal growth factor-like domain. Binding was not inhibited by low molecular weight urokinase or by a recombinant scu-PA missing amino acids 9-45. Cell-bound scu-PA migrated at its native molecular mass on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of plasminogen, scu-PA bound to endothelial cells generated greater plasmin activity than did scu-PA in the absence of cells. In contrast, when tcu-PA was added directly to HUVEC, sodium dodecyl sulfate-stable complexes formed with cell or matrix-associated plasminogen activator inhibitors with a loss of plasminogen activator activity. These studies suggest that endothelial cells in culture express high affinity binding sites for the epidermal growth factor domain of scu-PA. Interaction of scu-PA with these receptors may permit plasminogen activator activity to be expressed at discrete sites on the endothelial cell membrane.

Binding, Competitive↗

PubMed1990

Effects of in utero ethanol exposure on the developing dopaminergic system in rats.

Previous studies from this and other laboratories suggest that dopamine is decreased in selected brain regions of postnatal rats exposed to ethanol in utero. The present study expands previous work by examining the effects of in utero ethanol exposure on dopamine D1 and D2 binding sites and dopamine uptake in postnatal rats. In addition, dopamine content in the brain stem and frontal cortex of fetal and neonatal rats was examined. The experimental results indicate that in utero ethanol exposure markedly affects the postnatal development of the dopaminergic system in the striatum and frontal cortex. We observed a marked, transient deficiency of striatal dopamine (greater than 40% decrease at 19 days) and dopamine uptake sites (approximately 25% decrease in Vmax at 35 days). The Bmax for striatal dopamine D1 binding sites was decreased by greater than 20% at both 19 and 35 days. Cortical D1 sites were markedly decreased at 19 days (greater than 40%). In contrast, the number of striatal D2 receptors was unaffected by in utero ethanol exposure at both ages. Analysis of tissue from neonatal rats demonstrated a marked dopamine deficiency in ethanol-exposed rats on postnatal day 5. In light of the proposed morphogenic actions of dopamine early in development, it is possible that the early dopamine deficiency contributes to the abnormal postnatal development of the dopaminergic system.

Animals↗

PubMed1990

v-Ha-ras transgene abrogates the initiation step in mouse skin tumorigenesis: effects of phorbol esters and retinoic acid.

Experimental carcinogenesis has led to a concept that defines two discrete stages in the development of skin tumors: (i) initiation, which is accomplished by using a mutagen that presumably activates a protooncogene, and (ii) promotion, which is a reversible process brought about most commonly by repeated application of phorbol esters. We have created a transgenic mouse strain that carries the activated v-Ha-ras oncogene fused to the promoter of the mouse embryonic alpha-like, zeta-globin gene. Unexpectedly, these animals developed papillomas at areas of epidermal abrasion and, because abrasion can also serve as a tumor-promoting event in mutagen-treated mouse skin, we tested these mice for their ability to respond to phorbol ester application. Within 6 weeks virtually all treated carrier mice had developed multiple papillomas, some of which went on to develop squamous cell carcinomas and, more frequently, underlying sarcomas. We conclude that the oncogene "preinitiates" carrier mice, replacing the initiation/mutagenesis step and immediately sensitizing them to the action of tumor promoters. In addition, treatment of the mice with retinoic acid dramatically delays, reduces, and often completely inhibits the appearance of promoter-induced papillomas. This strain has use in screening tumor promoters and for assessing antitumor and antiproliferative agents.

Animals↗

PubMed1990

Cultured human luteal peripheral monocytes secrete increased levels of interleukin-1.

Interleukin-1 (IL-1), an immune monokine secreted by activated macrophages and monocytes, appears to be intimately involved in endocrine phenomena. It is well established that IL-1 mediates a number of immune and inflammatory responses. In addition, the production of IL-1 appears to be modulated by the gonadal estradiol and progesterone, leading to this study of IL-1 secretion by cultured peripheral monocytes isolated at varying times during the menstrual cycle and pregnancy. Circulating peripheral monocytes were isolated from eight women undergoing human menopausal gonadotropin-stimulated ovulation induction during the late follicular phase just before hCG administration and from eight similarly stimulated women on the 12th day after hCG administration. Peripheral monocytes were also isolated from six women during both second and third trimester pregnancy. After 48 h in culture, conditioned media were assayed for IL-1 bioactivity using the D1O lymphocyte proliferation assay. Significantly more IL-1 bioactivity was secreted by monocytes isolated in the luteal phase of the cycle (52.4 +/- 17.5 IU/mL) compared to that in late follicular phase (5.2 +/- 0.9 IU/mL; P = 0.001) or third trimester of pregnancy (7.0 +/- 1.5 IU/mL; P = 0.006). Thus, peripheral monocyte IL-1 secretion appears to be increased by luteal levels of progesterone, although further elevation of progesterone during pregnancy returns IL-1 levels to the preovulatory baseline. In addition, basal body temperatures obtained in four women during third trimester pregnancy were 98 F or less. Thus, IL-1 secretion from cultured monocytes appears to increase with luteal concentrations of progesterone and decrease to preovulatory levels at higher concentrations of the steroid during pregnancy, which may account for the dissociation of high progesterone levels and elevated basal body temperature during late pregnancy.

Adult↗

PubMed1990

Objective tinnitus of vascular origin with hearing improvement after treatment.

Objective tinnitus occurs as a result of muscular contraction or vascular pulsations. The literature is reviewed and we present two case reports of vascular objective tinnitus and its diagnostic and therapeutic modalities. One patient was treated with embolization alone; the other, with embolization and surgical ligation. Both patients achieved an improvement in sensorineural hearing thresholds in their affected ears; one patient experienced an improvement in speech reception threshold of 30 decibels. Measures useful to diagnosis and evaluation of therapy and reasons for the observed improved hearing thresholds are discussed.

Adult↗

PubMed1989

Synthesis and expression of C1 inhibitor by human umbilical vein endothelial cells.

The biologic activity of C1 esterase, activated forms of factor XII and kallikrein at sites of vascular inflammation may be regulated by C1 inhibitor (C1 INH) elaborated by endothelial cells. Therefore, we investigated whether human umbilical vein endothelial cells (HUVEC) in culture produce C1 INH. Passaged HUVEC contain 1.6 +/- 0.8 micrograms of C1 INH/10(8) cells (mean +/- S.D.; n = 7) which was immunochemically similar to plasma C1 INH measured by a competitive enzyme-linked immunosorbent assay. Methylamine-treated lysates of HUVEC contained a functional inhibitor of purified kallikrein (2.7 +/- 0.8 micrograms activity/10(8) cells, mean +/- S.D.; n = 4). The HUVEC-derived kallikrein inhibitory activity was mostly C1 INH because it was reversed by chemically treating the lysate with chloroform and was neutralized by anti-C1 INH antibody. A lysate of HUVEC derived from an umbilical cord from a patient with Type I hereditary angioedema contained less than 30% of the normal levels of C1 INH antigen and activity. Immunohistochemical staining of HUVEC demonstrated a diffuse pattern of staining for C1 INH. HUVEC C1 INH was also expressed on the endothelial cell surface as detected by binding of anti-C1 INH antibody to intact monolayers and was elaborated progressively into the overlying media over the first 24 h in culture. HUVEC incubated with [35S] methionine secreted a metabolically labeled protein having a molecular mass of 92 kDa immunoisolated using polyclonal or monoclonal antibodies to human C1 INH. A mRNA transcript encoding for C1 INH was detected by slot blot hybridization. Incubation of HUVEC with gamma-interferon stimulated the expression of the 2.1 kilobase mRNA for C1 INH and increased the level of C1 INH produced by these cells. Production and expression of C1 INH by endothelial cells may help modulate the complement system and the contact system of plasma proteolysis on the vascular surface in vivo.

Blotting, Northern↗

PubMed1988

The expression of high molecular weight kininogen on human umbilical vein endothelial cells.

High molecular weight kininogen (HMWK) functions as a cofactor for activation of plasma serine zymogens and as an inhibitor of tissue cysteine proteases. Cell surfaces to which HMWK binds may provide sites for regulation of these systems. Localization of these HMWK-dependent processes at sites of vascular injury may depend on its binding to specific receptors on endothelial cells. In culture, passaged human umbilical vein endothelial cells (HUVEC) bind anti-HMWK antibody to the cell surface and contain 171 +/- 75 ng of HMWK/10(8) cells. [35S]Methionine-labeled HUVEC in culture synthesize a 120-kDa protein immunoisolated using an anti-kininogen antibody, and a 3500-nucleotide message for human HMWK was detected by Northern blot in RNA extracted from HUVEC. HUVEC also express unoccupied binding sites for HMWK on their surface. 125I-HMWK specifically binds to HUVEC in a reaction requiring Zn2+. 125I-HMWK binding to HUVEC is saturable at 4 degrees C but not at 23 degrees C. 125I-HMWK binds to HUVEC with equal affinity as unlabeled HMWK. Kallikrein, factor XII, fibrinogen, fibronectin, and thrombin do not inhibit 125I-HMWK binding to HUVEC. 125I-HMWK-HUVEC binding remains fully reversible at 60 min following the addition of a 50-fold molar excess HMWK. HUVEC express 9.3 +/- 2.0 X 10(5) (mean +/- S.E.) HMWK binding sites/cell (Kd = 52 +/- 13 nM). Both added and cell-bound 125I-HMWK migrate at 120 kDa on sodium dodecyl sulfate gel electrophoresis, suggesting that the protein remains uncleaved upon binding to the HUVEC surface. These studies indicate that HUVEC synthesize HMWK and the HUVEC surface has a site for its expression. By synthesizing and localizing HMWK to the cell surface, endothelial cells may contribute to the activation of plasma's contact serine zymogens and regulation of tissue cysteine proteases.

Blotting, Northern↗

PubMed1988

Tissue-type plasminogen activator binding to human endothelial cells. Evidence for two distinct binding sites.

The endothelium may contribute to fibrinolysis through the binding of plasminogen activators or plasminogen activator inhibitors to the cell surface. Using a solid-phase radioimmunoassay, we observed that antibodies to recombinant tissue-type plasminogen activator (rt-PA) and plasminogen activator inhibitor type 1 (PAI-1) bound to the surface of cultured human umbilical vein endothelial cells (HUVEC). HUVEC also specifically bound added radiolabeled rt-PA with apparent steady-state binding being reached by 1 h at 4 degrees C. When added at low concentrations (less than 5 nM), rt-PA bound with high affinity mainly via the catalytic site, forming a sodium dodecyl sulfate-stable 105-kDa complex which dissociates from the cell surface over time and which could be immunoprecipitated by a monoclonal antibody to PAI-1. rt-PA bound to this high affinity site retained less than 5% of its expected plasminogen activator activity. At higher concentrations, binding did not require the catalytic site and was rapidly reversible. rt-PA initially bound to this site retained plasminogen activator activity. These studies suggest that tissue-type plasminogen activator and PAI-1 are expressed on the surface of cultured HUVEC. HUVEC also express unoccupied binding sites for exogenous tissue-type plasminogen activator. The balance between the expression of plasminogen activator inhibitors and these unoccupied binding sites for plasminogen activators on the endothelial surface may contribute to the regulation of fibrinolysis.

Binding Sites↗

PubMed1988

Gonadal steroids modulate human monocyte interleukin-1 (IL-1) activity.

Interleukin-1 (IL-1), a monocyte and macrophage product, is the mediator of a wide variety of immune responses, including fever, and increases during the luteal phase of the menstrual cycle, concomitantly with progesterone (P). These studies were undertaken to assess the possible relationship between steroidogenesis and IL-1 activity elaborated by human peripheral monocytes. IL-1 was measured with the D-10 thymocyte stimulation bioassay and dose response curves as a function of both estradiol (E2) and P were established. Low concentrations of both E2 (10(-9) M-10(-10) M) and P (10(-8) M-10(-9) M) resulted in maximal IL-1 stimulation. At higher concentrations of both E2 (10(-7) M) and P (10(-7) M-10(-5) M) there was a significant reduction (P less than 0.05) in IL-1 activity. However, neither E2 nor P production by human granulosa-luteal cells cultured with increasing amounts of human IL-1 (0 to 20 IU/ml) was affected in either the absence or presence of human chorionic gonadotropin (hCG, 5 IU/ml). Thus, human peripheral monocyte IL-1 activity appears to be modulated by gonadal steroids; however, a reciprocal relationship between IL-1 and gonadal steroidogenesis was not observed.

Animals↗

PubMed1986

Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development.

We have constructed a transgenic mouse strain in which a mammary tumor virus LTR/c-myc fusion gene is anomalously expressed in a wide variety of tissues. The deregulated c-myc transgene, now glucocorticoid inducible, contributes to an increased incidence of a variety of tumors, including those of testicular, breast, lymphocytic (B cell and T cell), and mast cell origin. The deregulated gene does not, however, otherwise disturb cell proliferation, nor does it interfere with normal development in these animals. Moreover, since not all tissues that express the transgene develop neoplasms, these results begin to define the transforming spectrum of the c-myc oncogene. They also extend to several organ systems the notion that elements in addition to an activated c-myc gene are required to induce malignancy in the living organism.

Adenocarcinoma↗