Biomedical subjects

Shingo Fujii

Publications and source records attributed to Shingo Fujii.

At least 19 recordsLinked to original sources

PubMed2005

Platelet-derived soluble factors induce human extravillous trophoblast migration and differentiation: platelets are a possible regulator of trophoblast infiltration into maternal spiral arteries.

In early pregnancy, human extravillous trophoblasts (EVTs) invade and remodel maternal arteries. We have previously demonstrated that CCR1 is expressed on perivascular/endovascular trophoblasts and that CCR1 ligands promote EVT migration. In this study, we examined the physiologic roles of platelet-derived chemoattractants on EVT invasion. By immunohistochemistry, maternal platelets were localized among endovascular trophoblasts within the lumen of spiral arteries. Extracellular matrices (ECMs) were also detected among endovascular trophoblasts and platelets, suggesting that the platelets in these arteries were activated by ECMs. In vitro, platelets attached to EVTs isolated from human villous explant cultures and expressed P-selectin on the cell surface. Platelets significantly enhanced migration of EVTs without affecting proliferation of EVTs or secretion of MMP-2 or MMP-9. The invasion-enhancing effect of platelet-derived culture medium on EVTs was neutralized by anti-CCR1 antibody. Heat treatment completely abrogated the invasion-promoting effects of platelet-derived culture medium, but charcoal stripping did not. Platelets also induced endovascular trophoblast-like morphologic changes and integrin alpha1 expression in EVTs during 48-hour culture. These findings suggest that maternal platelets activated in the spiral arteries can regulate trophoblastic vascular infiltration and differentiation by releasing various soluble factors.

Arteries↗

PubMed2005

Dysmenorrhea: evaluation with cine-mode-display MR imaging--initial experience.

PURPOSE: To prospectively evaluate uterine contractility during menstruation and its relation to primary dysmenorrhea by using magnetic resonance (MR) imaging with cine mode display. MATERIALS AND METHODS: The university ethics committee approved the study protocol, and all subjects gave written informed consent. Nineteen healthy women were examined during menstrual cycle days 1-3 by using a 1.5-T-magnet unit. Sixty serial half-Fourier rapid acquisition with relaxation enhancement MR images of the uterus were obtained every 3 seconds for 3 minutes and displayed in cine mode. MR images were analyzed in terms of thickness of the inner low-signal-intensity myometrial layer, presence of endometrial distortion, and uterine peristalsis detectability. Pain was assessed by using a four-point scale. For 56 MR imaging cases, the association between MR imaging findings and pain degree was examined with Spearman correlation and Mann-Whitney tests. MR imaging findings in the dysmenorrheic and eumenorrheic subject groups were compared by using Mann-Whitney and chi(2) tests. The area of the uterine myometrium in both groups was calculated for quantitative assessment of uterine contraction and was compared between the groups by using the Student t test. RESULTS: MR imaging findings revealed marked changes during cycle days 1-3. Thickness of the inner low-signal-intensity myometrial layer and endometrial distortion were significantly associated with pain degree (P < .001), while uterine peristalsis was undetectable when pain was severe or moderate. The area of the uterine myometrium significantly decreased during cycle days 1-3 in the dysmenorrheic group, as compared with that in the eumenorrheic group (P = .010). CONCLUSION: MR imaging features of the uterus on cycle days 1-3 correlated with pain degree. Cine-mode-display MR imaging is a potential tool for evaluating dysmenorrhea.

Adult↗

PubMed2005

Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells.

To investigate the effect of estrogen on neuronal differentiation, especially on dopaminergic (DA) neurons, human neural stem cells (NSCs) were differentiated in the presence of 17beta-estradiol. NSCs gave rise to tyrosine hydroxylase (TH)-positive neurons in vitro, the proportion of which was increased by 17beta-estradiol. Increase in TH-positive neurons was abrogated by an estrogen receptor (ER) antagonist, ICI182780, suggesting ERs play a role in differentiation of DA neurons. The observation that ERs were expressed in both proliferating NSCs and postmitotic DA neurons suggested that increase in TH-positive neurons was due to induction and support of DA neurons. 17beta-Estradiol also increased the number of DA neurons derived from human NSCs in vivo when the cells were grafted into mouse brains. These results support a possible role for estrogen in the transplantation of NSCs for Parkinson's disease.

Animals↗

PubMed2005

Posterior cul-de-sac obliteration associated with endometriosis: MR imaging evaluation.

PURPOSE: To retrospectively evaluate the accuracy of magnetic resonance (MR) imaging in depicting posterior cul-de-sac obliteration in patients with endometriosis. MATERIALS AND METHODS: Institutional review board approval was not required for this retrospective study, but informed consent was obtained from all patients. MR images obtained between January 1989 and December 2000 in 57 women (mean age, 39 years; age range, 26-52 years) with histologically confirmed endometriosis were retrospectively evaluated by four radiologists independently. All patients underwent laparotomy or laparoscopy less than 1 month after MR imaging. MR images were evaluated for the presence and location of endometrial implants and adhesions. MR images were also scored for the presence of five findings: retroflexed uterus, elevated posterior vaginal fornix, intestinal tethering or tethered appearance of rectum in direction of uterus, faint strands between uterus and intestine, and fibrotic plaque or nodule covering serosal surface of the uterus. Interobserver agreement for each of the five findings and for the overall diagnosis of cul-de-sac obliteration was calculated. Sensitivity, specificity, accuracy, positive and negative predictive values, and kappa statistics were determined. RESULTS: Laparotomy or laparoscopy revealed posterior cul-de-sac obliteration in 30 patients. Overall, the four radiologists had mean accuracies of 89.0% and 76.3% for diagnosing endometrial implants and adhesions, respectively, at MR imaging. Overall, the radiologists achieved mean sensitivity, specificity, accuracy, and positive and negative predictive values of 68.4%, 76.0%, 71.9%, 76.6%, and 68.5%, respectively, in diagnosing posterior cul-de-sac obliteration. The best accuracy (mean value, 64.5%) was obtained with the finding of fibrotic plaque in the uterine serosal surface. Readers agreed on the observations 63.2%-91.2% of the time. For the impression of the presence or absence of posterior cul-de-sac obliteration, interobserver agreement varied between substantial and moderate: Mean interobserver agreement was 78.4% (range, 70.2%-84.2%), and mean kappa was 0.57 (range, 0.40-0.67). Mean accuracy of MR imaging for diagnosing posterior cul-de-sac obliteration was 71.9%. CONCLUSION: These results suggest that use of the described MR imaging findings may enable diagnosis of posterior cul-de-sac obliteration.

Adult↗

PubMed2005

A semiautomated technique for evaluation of uterine peristalsis.

PURPOSE: To evaluate the capability of a newly developed semiautomatic analysis technique for evaluation of uterine peristalsis in comparison with visual assessment. MATERIALS AND METHODS: Cine magnetic resonance (MR) images were obtained from 16 normal volunteers in periovulatory phase. Sixty-eight studies were evaluated by both visual evaluation and by a semiautomated computer assisted software. The software was developed by applying an automated contour tracking method and enables objective analysis of frequency, amplitude, velocity, and direction. Assessments were based on: 1) the recognition of peristalsis, 2) peristaltic direction and frequency, and 3) the way of recognizing peristaltic direction. The data obtained by both modalities were compared with those of previously reported ultrasound (US) findings. RESULTS: Uterine peristalsis was identified in all studies by both objective and visual analyses. There was no significant difference in the identification of peristalsis, recognition of peristaltic directions, or peristaltic frequency (P > 0.05). Data were well in accordance with those in US literature. Peristaltic direction was recognized either by configuration change in the endometrium or by conduction of low signal intensity in the subendometrial myometrium and there was statistically no difference. CONCLUSION: Evaluation of uterine peristalsis by the semiautomatic analysis accorded well with the results obtained visual assessments and previous US findings.

Adult↗

PubMed2005

Uterine contractions evaluated on cine MR imaging in patients with uterine leiomyomas.

PURPOSE: Submucosal leiomyoma is one of the most recognized causes of infertility and habitual abortion. The purpose of this study is to evaluate uterine peristalsis, a cycle-related inherent contractility of uterus probably responsible for sperm transport and conservation of pregnancy, in patients with uterine leiomyomas using cine magnetic resonance (MR) imaging. MATERIALS AND METHODS: Study population consisted of 26 female patients (age range: 19-51 years, mean: 41 years), in which 16 patients had submucosal leiomyomas and 10 patients had intramural or subserosal leiomyomas. We prospectively performed MR imaging of the midsagittal plane of uterus using 1.5 T magnet (Symphony, Siemens Medical Systems) with a body array coil, and obtained 60 half-Fourier acquisition single shot turbo spin echo (HASTE) images (Echo time=80 ms, FOV=300 mm, slice thickness 5 mm, matrix 256x256) within 2 min, and displayed them on cine mode at 12x faster than real speed. Evaluated were peristaltic movements at the endometral-myometrial junction and focal myometrial movements, adjacent to leiomyomas, regarding presence, direction, frequency, and conduction. RESULTS: The peristaltic movements were identified in 12/16 patients with submucosal lesions and 10/10 with other leiomyomas. The frequency and direction were cycle-related. Loss of peristalsis was noted adjacent to submucosal myomas in 4/12 patients, but was not in others. Focal myometrial movements were noted in 9/16 patients with submucosal myomas, but not in others. CONCLUSIONS: Uterine peristaltic movements were partly interrupted by submucosal leiomoymas, but not by myometrial or subserosal leiomyomas. Loss of peristalsis and focal myometrial movements was noted only adjacent to submucosal leiomyomas. These findings are considered to represent dysfunctional contractility, and may be related with pregnancy loss.

Adult↗

PubMed2004

In vivo anti-tumor effect of dual release of cisplatin and adriamycin from biodegradable gelatin hydrogel.

The objective of this paper is to investigate the in vivo anti-tumor effect by dual release of cisplatin (CDDP) and adriamycin (ADM) from a biodegradable hydrogel. Hydrogels with different water contents were prepared through the chemical crosslinking of gelatin by various concentrations of glutaraldehyde. Aqueous solution of CDDP, ADM or their mixture (CDDP+ADM) was impregnated into the freeze-dried hydrogel, followed by air-drying to obtain the dried hydrogel incorporating the corresponding drug. Irrespective of the hydrogel water content, 8-20% of CDDP incorporated and 60-80% of ADM was released from the hydrogel in the phosphate-buffered saline solution (PBS) at 37 degrees C within the initial 6 h and thereafter little release was observed. When intratumorally applied into mice carrying a mass of Meth-AR-1 tumor cells, the hydrogel incorporating CDDP+ADM showed significant higher anti-tumor effect on the tumor growth suppression and on survival period than other drug applications. Combination effect assay revealed that the hydrogel incorporating CDDP+ADM showed a synergistic effect between the CDDP and ADM, while the solution form showed antagonistic. The concentration of CDDP and ADM in the tumor tissue maintained at higher levels over 14 days after application. The time course of in vivo CDDP retention was in a good accordance with that of hydrogel remaining, whereas ADM was released faster, followed by the sustained release for 14 days. No practically problematic change in the mouse body and blood biochemical parameters was observed by application of the hydrogel incorporating CDDP+ADM. We conclude that dual sustained release of CDDP and ADM attached to the tumor synergistically enhanced their in vivo anti-tumor effect through the trans-tissue delivery.

Animals↗

PubMed2004

Defining the position of the switches between replicative and bypass DNA polymerases.

Cells contain specialized DNA polymerases that are able to copy past lesions with an associated risk of generating mutations, the major cause of cancer. Here, we reconstitute translesion synthesis (TLS) using the replicative (Pol III) and major bypass (Pol V) DNA polymerases from Escherichia coli in the presence of accessory factors. When the replicative polymerase disconnects from the template in the vicinity of a lesion, Pol V binds the blocked replication intermediate and forms a stable complex by means of a dual interaction with the tip of the RecA filament and the beta-clamp, the processivity factor donated by the blocked Pol III holoenzyme. Both interactions are required to confer to Pol V the processivity that will allow it synthesize, in a single binding event, a TLS patch long enough to support further extension by Pol III. In the absence of these accessory factors, the patch synthesized by Pol V is too short, being degraded by the Pol III-associated exonuclease activity that senses the distortion induced by the lesion, thus leading to an aborted bypass process.

DNA Damage↗

PubMed2004

Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells.

Naturally occurring CD25(+)CD4(+) regulatory T cells are engaged in the maintenance of immunological self-tolerance and down-regulation of various immune responses. Recent studies with mice showed that Foxp3, which encodes the transcription factor Scurfin, is a master regulatory gene for the development and function of CD25(+)CD4(+) regulatory T cells. Here we examined the role of FOXP3 in human CD25(+)CD4(+) regulatory T cells. The FOXP3 gene and its protein product were preferentially expressed in peripheral CD25(+)CD4(+) T cells, in particular CD25(+)CD45RO(+)CD4(+) T cells in normal individuals and, interestingly, in some human T cell leukemia virus type 1-infected T cell lines, which constitutively express CD25. TCR stimulation of CD25(-)CD45RO(-)CD4(+) naive T cells failed to elicit FOXP3 expression at the gene or protein level. Ex vivo retroviral gene transfer of FOXP3, on the other hand, converted peripheral CD25(-)CD45RO(-)CD4(+) naive T cells into a regulatory T cell phenotype similar to CD25(+)CD4(+) regulatory T cells. For example, FOXP3-transduced T cells exhibited impaired proliferation and production of cytokines including IL-2 and IL-10 upon TCR stimulation, up-regulated the expression of regulatory T cell-associated molecules such as CD25 and CTL-associated antigen-4 and suppressed in vitro proliferation of other T cells in a cell-cell contact-dependent manner. Thus, human FOXP3 is a crucial regulatory gene for the development and function of CD25(+)CD4(+) regulatory T cells, and can be used as their reliable marker. Furthermore, regulatory T cells de novo produced from normal naive T cells by FOXP3 transduction can be instrumental for treatment of autoimmune/inflammatory diseases and negative control of various immune responses.

Autoimmune Diseases↗

PubMed2004

Increased expression of calcium-binding protein S100 in human uterine smooth muscle tumours.

S100 proteins belong to the EF-hand Ca(2+ )-binding protein family and regulate a variety of cellular processes via interaction with different target proteins. Several diseases, including cancer and melanoma, are related to the abnormal expression of S100 proteins, which are expressed in cell- and tissue-specific manners. We investigated the expression of S100 family members in human uterine smooth muscle tumours. Expression of six members of the S100 protein family: S100A1, A4, A6, A7, A10 and A11, was found in human uterine leiomyoma and myometrium tissue, but expression of other members was not detected by RT-PCR. Real-time PCR showed that S100A11 expression was significantly increased in leiomyoma compared with myometrium. Suppression of S100A11 by small interfering RNA (siRNA) led to apoptosis, and the overexpression of S100A11 inhibited apoptosis in human uterine smooth muscle tumour cells. These findings suggest that S100A11 has an anti-apoptotic function and is related to the process of growth of human uterine leiomyoma.

Cell Line, Tumor↗

PubMed2004

The biochemical requirements of DNA polymerase V-mediated translesion synthesis revisited.

In addition to replicative DNA polymerases, cells contain specialized DNA polymerases involved in processes such as lesion tolerance, mutagenesis and immunoglobulin diversity. In Escherichia coli, DNA polymerase V (Pol V), encoded by the umuDC locus, is involved in translesion synthesis (TLS) and mutagenesis. Genetic studies have established that mutagenesis requires both UmuC and a proteolytic product of UmuD (UmuD'). In addition, RecA protein and the replication processivity factor, the beta-clamp, were genetically found to be essential co-factors for mutagenesis. Here, we have reconstituted Pol V-mediated bypass of three common replication-blocking lesions, namely the two major UV-induced lesions and a guanine adduct formed by a chemical carcinogen (G-AAF) under conditions that fulfil these in vivo requirements. Two co-factors are essential for efficient Pol V-mediated lesion bypass: (i) a DNA substrate onto which the beta-clamp is stably loaded; and (ii) an extended single-stranded RecA/ATP filament assembled downstream from the lesion site. For efficient bypass, Pol V needs to interact simultaneously with the beta-clamp and the 3' tip of the RecA filament. Formation of an extended RecA/ATP filament and stable loading of the beta-clamp are best achieved on long single-stranded circular DNA templates. In contrast to previously published data, the single-stranded DNA-binding protein (SSB) is not absolutely required for Pol V-mediated lesion bypass provided ATP, instead of ATPgammaS, activates the RecA filament. Further discrepancies with the existing literature are explainable by the use of either inadequate DNA substrates or a UmuC fusion protein instead of native Pol V.

Adenosine Triphosphate↗

PubMed2004

Cyclic mechanical stretch augments both interleukin-8 and monocyte chemotactic protein-3 production in the cultured human uterine cervical fibroblast cells.

Intensive local leukocyte infiltration in the uterine cervix is a characteristic feature in the process of cervical ripening. The infiltrated leukocytes include neutrophils, macrophages and monocytes, which are believed to play important roles in cervical ripening by secreting elastase, matrix metalloproteinase and interleukin-1 (IL-1). Interleukin-8 (IL-8) and monocyte chemotactic protein-3 (MCP-3) belong to the CXC and CC chemokine families, and mediate the chemotaxis of neutrophils and monocytes/macrophages respectively. The aim of the present study was to investigate the possible involvement of IL-8 and MCP-3 in leukocyte chemotaxis in cervical ripening. Immunohistochemistry and RT-PCR detected both IL-8 and MCP-3 expression in human pregnant uterine cervices. Labour-like cyclic mechanical stretch for 48 h significantly elevated both IL-8 (555%) and MCP-3 (360%) secretion from cultured human uterine cervical fibroblast (CxF) cells (P<0.05 for both). Cyclic mechanical stretch for 24, 36 and 48 h significantly increased both IL-8 and MCP-3 mRNA expression in CxF cells (P<0.05 for all). The stretch-induced augmentation of both IL-8 and MCP-3 expression was significantly suppressed by an activator protein-1 (AP-1) inhibitor, curcumin. These data suggest that cyclic mechanical stretch of the uterine cervix by the presenting part of the fetus during labour may augment both IL-8 and MCP-3 production in the uterine cervix via AP-1 activation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Neural precursor cells derived from human embryonic brain retain regional specificity.

Recent studies have revealed that neural precursor cells can be expanded not only from the subventricular zone and hippocampus but also from other regions of the human embryonic brain. To determine the regional differences of these precursor cells, we divided the brain of a 9-week-old human embryo into four parts, i.e., telencephalon, diencephalon, mesencephalon, and rhombencephalon. All cultures of the tissues yielded neurospheres, and these spheres gave rise to neurons, astrocytes, and oligodendrocytes. An analysis of clonal populations revealed that these precursor cells were multipotent, and two region-specific differences in neural precursor cells were revealed: 1) The precursor cells from the rostral part of the brain tended to proliferate faster than those from the caudal part, and 2) the precursor cells from the diencephalon and mesencephalon gave rise to more tyrosine hydoxylase (TH)-positive neurons than those from the telencephalon and rhombencephalon. When 50-day-cultured spheres were caused to differentiate, the percentage of TH-positive cells per total cell population was 1.2% for diencephalic and mesencephalic precursors, whereas it was 0.4% for telencephalic and rhombencephalic ones. Furthermore, the TH-positive cells from diencephalic and mesencephalic precursors were large, multipolar, and gamma-aminobutyric acid (GABA)-negative, which suggested that these cells were midbrain dopaminergic neurons. In contrast, TH-positive cells from telencephalic and rhombencephalic precursors were small, bipolar, and GABA-positive. These results suggest that human neural precursor cells might have the potential to differentiate into a variety of cells but retain regional specificity.

Animals↗

PubMed2004

Structural and biochemical analysis of sliding clamp/ligand interactions suggest a competition between replicative and translesion DNA polymerases.

Most DNA polymerases interact with their cognate processive replication factor through a small peptide, this interaction being absolutely required for their function in vivo. We have solved the crystal structure of a complex between the beta sliding clamp of Escherichia coli and the 16 residue C-terminal peptide of Pol IV (P16). The seven C-terminal residues bind to a pocket located at the surface of one beta monomer. This region was previously identified as the binding site of another beta clamp binding protein, the delta subunit of the gamma complex. We show that peptide P16 competitively prevents beta-clamp-mediated stimulation of both Pol IV and alpha subunit DNA polymerase activities, suggesting that the site of interaction of the alpha subunit with beta is identical with, or overlaps that of Pol IV. This common binding site for delta, Pol IV and alpha subunit is shown to be formed by residues that are highly conserved among many bacterial beta homologs, thus defining an evolutionarily conserved hydrophobic crevice for sliding clamp ligands and a new target for antibiotic drug design.

Binding, Competitive↗

PubMed2004

Human extravillous trophoblasts express laeverin, a novel protein that belongs to membrane-bound gluzincin metallopeptidases.

Human extravillous trophoblasts (EVTs) invade the maternal decidua. To identify the molecules involved in EVT invasion, we raised a murine monoclonal antibody (CHL2) that reacts with human EVTs. The molecular mass of CHL2 antigen purified from placental tissues was 160 kDa. Although the N-terminal partial amino acid sequence and one internal sequence are still unreported, the other three internal sequences matched those deduced from the coding region of the estimated sequence tag (1672 bp, AK075131). Based on this information, the full-length of the coding cDNA sequence of CHL2 antigen (2970 bp), which has not been reported elsewhere, was determined by 5' RACE. This novel protein, named laeverin, has a peptidase M1 motif containing a zinc-binding active site. It also has a transmembrane domain near the N-terminus. Its amino acid sequence is homologous with aminopeptidase N. These data indicate that human EVTs express laeverin, a novel protein belonging to gluzincin metallopeptidases.

Amino Acid Motifs↗

PubMed2004

Phenotypic variability in human embryonic holoprosencephaly in the Kyoto Collection.

BACKGROUND: Holoprosencephaly (HPE) is one of the most common developmental disorders of the brain associated with specific craniofacial dysmorphogenesis. Although numerous postnatal cases have been reported, early phases of its pathogenesis are not well understood. We examined over 200 cases of HPE human embryos both grossly and histologically, and studied their phenotypic variability and stage-specific characteristics. METHODS: Among over 44,000 human embryos in the Kyoto Collection of Human Embryos, 221 embryos have been diagnosed as HPE. Their developmental stages ranged from Carnegie stage (CS) 13 to CS 23. They were examined grossly and were also serially sectioned for detailed histological analysis. RESULTS: HPE embryos after CS 18 were classified into complete (true) cyclopia, synophthalmia (partially fused eyes in a single eye fissure), closely apposed separate eyes (possible forerunners of ethmocephaly and cebocephaly), and milder HPE with median cleft lip (premaxillary agenesis). At CS 13-17, when facial morphogenesis is not completed, HPE embryos had some facial characteristics that are specific to these stages and different from those in older HPE embryos. The midline structures of the brain, including the pituitary gland, were lacking or seriously hypoplastic in HPE embryos. Complete cyclopia was found in two cases after CS 18 but none at earlier stages. CONCLUSIONS: The early development of HPE in human embryos was systematically studied for the first time. The pathogenesis of craniofacial abnormalities, especially eye anomalies, in HPE was discussed in the light of recent studies with mutant laboratory animals.

Embryonic Development↗

PubMed2004

Uterine peristalsis: comparison of transvaginal ultrasound and two different sequences of cine MR imaging.

PURPOSE: To compare uterine peristalsis as seen on two different magnetic resonance (MR) imaging sequences and transvaginal ultrasound (TVUS), so as to better determine the best method for evaluating uterine peristalsis. MATERIALS AND METHODS: Eleven women in the periovulatory phase of the menstrual cycle underwent TVUS and cine MR imaging within a time period of three hours. Findings on cine MR images obtained with a serial 60 half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence and a 300 true fast imaging with steady-state precession (FISP) sequence were compared with TVUS. RESULTS: The image quality of the HASTE technique was the best among the three methods, followed by TVUS, and then true FISP technique (P < 0.001). Uterine peristalsis was detected in 100% of subjects using HASTE, 82% with True FISP, and 100% with TVUS. With HASTE technique, true FISP, and TVUS, respectively, endometrial stripping movement was identified in 100%, 82%, and 100%; direction was identified in 100%, 45% (P = 0.014), and 73%; and wave conduction toward the outer myometrium was identified in 55%, 9% (P = 0.025), and 0% (P = 0.014). CONCLUSION: Cine MR imaging by HASTE technique with a time resolution of two seconds best delineated uterine peristalsis compared to that by true FISP technique or with TVUS.

Adult↗

PubMed2004

Expression of the mitogen-inducible gene-2 (mig-2) is elevated in human uterine leiomyomas but not in leiomyosarcomas.

To investigate the role of a recently cloned cell proliferation-related gene, mig-2 (mitogen-inducible gene-2), in the growth of uterine leiomyomas, this gene's expression at mRNA and protein levels was examined in normal myometrium, leiomyomas, and leiomyosarcomas of the uterus. Northern blotting, Western blotting, and immunohistochemical staining demonstrated that mig-2 expression was increased in leiomyomas compared with normal myometrium, especially during the secretory phase of the menstrual cycle. In contrast, the mig-2 expression was greatly decreased in leiomyosarcomas. Direct sequencing of the whole coding region of mig-2 cDNA and Southern blotting revealed that mig-2 alterations, such as mutations, rearrangement, and amplification, were not present in either leiomyomas or leiomyosarcomas. These findings suggest that mig-2 expression is transcriptionally elevated in leiomyomas and could be involved in its hormone-mediated growth of leiomyomas of the uterus.

Basic Helix-Loop-Helix Proteins↗