UMLS:C0035412 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0035412 (rhabdomyosarcoma)
6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cell line (SCMC-MM-1) was established from a human abdominal tumor that was initially diagnosed as a malignant mesenchymoma by histological, immunohistochemical and clinical criteria. The cell line was composed of 2 morphologically and immunohistochemically distinct cell types, one with a small polygonal phenotype (P-type), characterized by the immunostaining of vimentin and the presence of a few electron-microscopically visible organelles, and the other with a giant tubular phenotype (T-type), characterized by the immunostaining of desmin, alpha-sarcomeric actin and skeletal-muscle myosin, and the presence of thick and thin myofilaments and Z-line materials. The parental cell line was cloned into 2 sublines, a P-type clone (SCMC-MM-1-19P) and a T-type clone (SCMC-MM-1-1T), which shared both 2q37 and 11p15 translocations, the characteristic chromosomal aberrations for rhabdomyosarcoma, with the parental SCMC-MM-1 cell line. Northern-blot analyses of the myogenic regulatory genes, including MyoD1 and myogenin, demonstrated the expression of MyoD1 in both of these sublines. Myogenin was very weakly expressed in the SCMC-MM-1-19P subline, but strongly expressed in the SCMC-MM-1-1T subline. Chromosomal and myogenic-regulatory-gene analyses revealed that both of these sublines were rhabdomyosarcoma cell lines. Furthermore, the regulatory-gene analyses indicated that these 2 sublines represented 2 distinct differentiation stages of myoblasts, and that MyoD1 and myogenin could serve as the lineage marker and the differentiation marker, respectively, of human rhabdomyosarcoma.
...
PMID:Differential expression of myogenic regulatory genes, MyoD1 and myogenin, in human rhabdomyosarcoma sublines. 131 1

Two clonal rat rhabdomyosarcoma cell lines BA-Han-1B and BA-Han-1C with different capacities for myogenic differentiation have been examined for the expression of muscle regulatory basic helix-loop-helix (bHLH) proteins of the MyoD family. Whereas cells of the BA-Han-1C subpopulation constitutively expressed MyoD1 and could be induced to differentiate with retinoic acid (RA), BA-Han-1B cells did not express any of the myogenic control factors and appeared to be largely differentiation-defective. Upon induction with RA, BA-Han-1C cells expressed also myogenin, in contrast to BA-Han-1B cells which never activated any of the genes encoding muscle bHLH factors. The onset of myogenin transcription in BA-Han-1C cells required de novo protein synthesis and DNA replication suggesting that RA probably did not act directly on the myogenin gene. Although MyoD1 was expressed in proliferating BA-Han-1C myoblasts, muscle-specific reporter genes were not activated indicating that MyoD was biologically inactive. However, transfections with plasmid expressing additional MyoD1 protein resulted in the transactivation of muscle genes even in the absence of RA. mRNA encoding the negative regulatory HLH protein Id was expressed in proliferating BA-Han-1C cells and disappeared later after RA induction which suggested that it may be involved in the regulation of MyoD1 activity. The myogenic differentiation of malignant rhabdomyosarcoma cells strictly correlated with the activation of the myogenin gene. In fact, stable transfections of BA-Han-1C cells with myogenin expressing plasmids resulted in spontaneous differentiation. Together, our results suggest that the transformed and undifferentiated phenotype of BA-Han-1C rhabdomyosarcoma cells is associated with the inactivation of the myogenic factor MyoD1 as well as lack of myogenin expression. RA alleviates the inhibition of myogenic differentiation, probably by activating MyoD protein and myogenin gene transcription. BA-Han-1B cells did not respond to RA and the differentiated phenotype could not be restored by overexpression of MyoD1 or myogenin.
...
PMID:Retinoic acid induces myogenin synthesis and myogenic differentiation in the rat rhabdomyosarcoma cell line BA-Han-1C. 132 66

The control of myogenin (Myf-4), one of the muscle-specific regulatory proteins, is particularly interesting since its expression appears obligatory in myoblasts at the onset of differentiation. We isolated the human Myf-4 (myogenin) gene and determined promoter elements which direct cell type-specific expression and are subject to transactivation by the muscle transcription factors Myf-5 and MyoD1 in fibroblasts. Extrinsic signals such as serum components and purified growth factors or potential intracellular signals such as cAMP down-regulate transcription of the myogenin gene. Constitutive expression of the catalytic subunit of PKA completely suppresses transactivation of the myogenin promoter by Myf-5 or MyoD1 suggesting that cAMP may act via phosphorylation by PKA. In contrast to normal myogenic cell lines in which differentiation and myogenin expression can be induced by the removal of serum components, retinoic acid (RA) is required for differentiation in the rat rhabdomyosarcoma cell line BA-Han-1C. This model system was utilized to investigate factors which influence the balance between the transformed state and differentiation. Administration of retinoic acid to BA-Han-1C cells leads to the accumulation of myogenin mRNA approximately 48 h after the addition of RA. This late induction requires ongoing protein- and DNA-synthesis suggesting that trans- and cis-acting factors may be involved in the control. The critical involvement of myogenin in the process of terminal muscle differentiation was also demonstrated in the rat L6 muscle cell line which has been blocked for differentiation by the transforming protein E1a of Ad5 adenovirus. In cells which stably express E1a, myogenin expression is completely suppressed while Myf-5 continues to be synthesized normally. However, E1a inhibits the transactivator function of Myf-5, as demonstrated on GAL4-Myf5 chimeric proteins. A possible interpretation of this result is that Myf-5 or factors activated by Myf-5 are required for the expression of myogenin and myogenin itself is necessary for the terminal differentiation of myoblasts.
...
PMID:Regulation of myogenin expression in normal and transformed myogenic cell lines. 134 Oct 49

Rhabdomyosarcomas (RMS) bear a morphological resemblance to developing striated muscle. It has been reported that two histologically distinct subtypes of RMS, embryonal and alveolar, behave differently in many clinical aspects, such as age distribution, primary site, and prognosis. We have investigated the expression of various genes, which are preferentially expressed in normal muscle tissue or cell culture (actins, myosins, and creatine kinases, and myogenic regulatory genes MyoD, myogenin, MRF4, and Myf5), in embryonal and alveolar subtypes and compared the results to the stages of developing human fetal limb muscle. The data showed that each of the RMS tumors tested, regardless of histological features, expressed MyoD1 and MRF4 transcripts. Expression of the myogenin gene was detectable in all alveolar RMS (n = 8), whereas only 5 of 8 embryonal RMS expressed myogenin transcripts. Trace levels of Myf5 transcripts were visible in all alveolar RMS and 7 of 8 embryonal RMS. The alpha-skeletal, alpha-cardiac, and beta- and gamma-cytoplasmic actin transcripts were detectable in all alveolar RMS. While the beta- and gamma-cytoplasmic actin transcripts were evident in all embryonal RMS, only 3 of 8 and 6 of 8 embryonal RMS expressed detectable levels of alpha-skeletal and alpha-cardiac actin transcripts, respectively. The embryonic form of myosin heavy chain was detectable in 1 of 8 of each type of tumor. Myosin light chain-1/3 transcripts were detectable in 4 of 8 alveolar RMS and 5 of 8 embryonal RMS. Brain creatine kinase transcripts were detectable in all alveolar RMS and 4 of 8 embryonal RMS, whereas none of the RMS samples contained detectable levels of the muscle form of creatine kinase. A comparison of the expression profiles with those of normal developing human fetal limb muscle (from 7.5 to 24 weeks' gestation) suggested that RMS resembled a relatively restricted segment of fetal muscle development. Furthermore, the data also showed a great deal of overlap in the differentiation state achieved by the embryonal and alveolar subtypes of RMS, suggesting that the clinicopathological difference between these two may not be due to malignant transformation of the cells from different positions in the normal pathway of myogenesis.
...
PMID:Muscle-specific gene expression in rhabdomyosarcomas and stages of human fetal skeletal muscle development. 171 37

The distinction of rhabdomyosarcoma (RMS) from other small blue round cell tumors of childhood, such as Ewing's sarcoma/peripheral primitive neuroectodermal tumor (pPNET) and neuroblastoma, continues to present a diagnostic challenge to pathologists. The recent recognition of the master role of myogenic regulatory proteins in skeletal muscle commitment and differentiation, and the availability of monoclonal antibodies to two of them (myogenin and MyoD1), has prompted us to test their diagnostic utility in routinely processed, formalin-fixed, and deparaffinized tissue. Preliminary studies had demonstrated that, with the use of heat-induced epitope retrieval techniques, expression of myogenin and MyoD1 could be documented specifically in nuclei of fetal skeletal muscle by the respective antibodies. We performed a retrospective immunohistochemical analysis on 72 cases of small blue round cell tumors, including 33 RMSs, 1 metastatic myogenous Wilms' tumor, 26 Ewing's sarcomas/pPNETs, and 12 neuroblastomas. Nuclear expression of myogenin and MyoD1 were both found in 30/33 non-overlapping cases of RMS, with no significant differences in the sensitivity with respect to histological subtypes, and in 1/1 case of myogenous Wilms' tumor. None of the neuroblastomas or Ewing's sarcomas/pPNETs demonstrated positive nuclear staining with either antibody. However, most of the neuroblastomas, and occasional Ewing's sarcomas/pPNETs, showed variable fibrillary, cytoplasmic immunoreactivity with antibody to MyoD1. We conclude that, with the use of microwave-based epitope retrieval, antibodies to myogenin and MyoD1 are both useful markers for the identification of RMS among other small blue round cell tumors of childhood, but antibodies to myogenin have technical advantages over those to MyoD1, as the latter may cross-react with an unknown cytoplasmic antigen in non-muscle cells and tumors.
...
PMID:Expression of myogenic regulatory proteins (myogenin and MyoD1) in small blue round cell tumors of childhood. 749 4

Human rhabdomyosarcoma RD cells express the myogenic regulatory factors MyoD and myogenin but differentiate spontaneously very poorly. Prolonged treatment of RD cells with the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA) induces growth arrest and myogenic differentiation as shown by the accumulation of alpha-actin and myosin light and heavy chains, without affecting the expression of MyoD and myogenin. In this study, we show that short-term phorbol ester treatment of the cultures is sufficient to trigger myogenic differentiation but not growth arrest. Furthermore, PKC inhibitors, such as staurosporine or calphostin C, prevent TPA-induced differentiation but not cell growth arrest. These data suggest that the two events are mediated by different pathways; a possible interpretation is that the activation of one or more PKC isoforms mediates the induction of differentiation, whereas the down-regulation of the same or different isoforms mediates the growth arrest. To address the mechanism whereby TPA affects cell growth and differentiation in RD cells, we first analyzed PKC isoenzyme distribution. We found that RD cells express the alpha, beta 1, gamma, and sigma PKC isoenzymes. Only the alpha isoform is exclusively found in the soluble fraction, but it translocates to the membrane fraction within 5 min of TPA treatment and is completely down-regulated after 6 h. The other isoenzymes are found associated to both the soluble and the particulate fractions and are down-regulated after long-term TPA treatment. By immunofluorescence analysis, we show that the PKC alpha down-regulation is specific for those cells that respond to TPA by activating the muscle phenotype. We propose that TPA-induced differentiation in RD cells is mediated by the transient activation of PKC alpha, which activates some of the intracellular events that are necessary for MyoD and myogenin transacting activity and for the induction of terminal differentiation of RD cells. By contrast, the constitutively active beta 1 and sigma are responsible for the maintenance of cell growth, and their down-regulation is responsible for long-term TPA-induced cell growth arrest.
...
PMID:Rapid activation and down-regulation of protein kinase C alpha in 12-O-Tetradecanoylphorbol-13-acetate-induced differentiation of human rhabdomyosarcoma cells. 754 6

Pax3 is an evolutionarily conserved transcription factor expressed in the lateral dermomyotome, a region that gives rise to limb muscle progenitors. Mutations in Pax-3 account for the mouse mutant Splotch which develops without limb musculature. We demonstrate that Pax3 can inhibit myogenic differentiation of C2C12 myoblasts normally induced by exposure to low serum. Specific missense mutations that affect the DNA binding characteristics of the two distinct DNA binding domains of Pax3 abolish this effect. Furthermore, we show that Pax3 can inhibit myogenic differentiation of 10T1/2 fibroblasts transfected with MyoD, but not of 10T1/2 cells transfected with myogenin. This anti-myogenic property is shared by a PAX3-forkhead fusion protein resulting from a t(2;13) chromosomal translocation found in pediatric alveolar rhabdomyosarcomas. These results suggest that Pax3 may suppress the terminal differentiation of migrating limb myoblasts and that the PAX3-forkhead fusion may contribute to the phenotype of alveolar rhabdomyosarcoma by preventing terminal differentiation.
...
PMID:Pax3 inhibits myogenic differentiation of cultured myoblast cells. 774 14

BA-Han-1C rat rhabdomyosarcoma cells grow with a transformed phenotype and do not differentiate efficiently. Here, we report that these cells can be induced with pertussis toxin (PTX) to rapidly express the myogenin gene and form terminally differentiated myotubes. Potential targets for the effect mediated by PTX are G alpha i-2 and G alpha i-3 proteins, the only inhibitor GTP-binding proteins expressed in these cells. While G alpha i-2 is found at the plasma membrane, G alpha i-3 is predominantly associated with Golgi vesicles and endoplasmic reticulum, suggesting that it may regulate protein trafficking. Differentiation of BA-Han-1C cells can also be induced by suramin, heparin, and other polyanions. As these compounds bind certain peptide growth factors, we assume that differentiation of BA-Han-1C cells is blocked by pathways involving autocrine or paracrine acting growth stimulating peptides. We present evidence that bFGF and cAMP inhibit induced differentiation in BA-Han-1C cells similar to normal myogenic cell lines, suggesting that signaling pathways mediated by these compounds are unaltered.
...
PMID:Differentiation of BA-HAN-1C rhabdomyosarcoma cells is controlled by a pertussis toxin sensitive signaling pathway. 829 37

There has been persistent controversy regarding the nature of cell differentiation in alveolar soft-part sarcoma (ASPS) since its first description in 1952. Some studies suggest that ASPS might represent an unusual variant of skeletal muscle tumor. Given the availability of new monoclonal antibodies to probe for skeletal muscle differentiation and the rapid advance in immunocytochemical techniques for deparaffinized, formalin-fixed tissue sections, we wished to test the proposed hypothesis that ASPS might represent a new type of rhabdomyosarcoma. Twelve archival samples of ASPS were retrieved, and we investigated the expression of two myogenic regulatory proteins, MyoD1 and myogenin, as well as other muscle-associated proteins, using sensitive immunocytochemical techniques. Despite the presence of desmin immunostaining in six ASPSs, no tumors were positive for either muscle actin or myoglobin. Most importantly, no specimen showed nuclear expression of MyoD1 or myogenin. In 11 tumors, however, there was considerable granular immunostaining in the tumor cell cytoplasm with the anti-MyoD1 monoclonal antibody 5.8A, a phenomenon observed in various nonmuscle normal and neoplastic tissues with this antibody. To analyze the exact nature of immunostaining of MyoD1 and desmin in ASPS, biochemical analyses using available fresh frozen tumor tissue were performed. Although a 53-kDa band was noted with antidesmin antibody on Western blot analysis, no specific protein band that corresponds to the 45-kDa MyoD1 was detected with antibody 5.8A. These results confirm the presence of desmin in ASPS but argue against authentic expression of MyoD1. They also suggest that the cytoplasmic immunostaining observed with anti-MyoD1 antibody 5.8A most likely represents a nonspecific cross-reaction with an unknown cytoplasmic antigen. Considering the master role that MyoD1 and myogenin play in skeletal muscle commitment and differentiation and the lack of expression of these two proteins in ASPS as determined immunocytochemically and biochemically, we think that the histogenesis of ASPS remains unknown.
...
PMID:Does alveolar soft-part sarcoma exhibit skeletal muscle differentiation? An immunocytochemical and biochemical study of myogenic regulatory protein expression. 873 64

Rhabdomyosarcoma is a tumor of skeletal muscle origin affecting children and young adults. Although relatively undifferentiated, cell lines derived from this tumor express myogenic regulatory factors and so may be useful models of abortive myogenic differentiation. In the present studies, we have determined the effect of increased intracellular cAMP on proliferation, morphologic differentiation, and expression of myogenic genes in the prototypic embryonal rhabdomyosarcoma cell line, RD. Whereas growth in dibutyryl cAMP (dbcAMP), forskolin, or butyrate led to morphologic differentiation, growth in dbcAMP inhibited proliferation, while growth in butyrate slowed but did not stop cell division. Expression of the genes for myogenin and myosin light chain was inhibited by dbcAMP, while butyrate decreased myogenin and increased myosin light chain transcription. MyoD and MRF4 expression was not altered under either condition and no myf5 expression was detected. We also determined the effects of dbcAMP and butyrate on total protein expression, as well as on a panel of muscle- and neural-specific proteins using functional assays, immunohistochemistry, and immunoprecipitation. The total protein levels of cells treated with either agent were double those of untreated cells. DbcAMP increased the activity of acetylcholinesterase (AChE) up to 10-fold compared to untreated cells, while butyrate had a substantially lesser effect. These increases were due to increased AChE protein synthesis and stability in dbcAMP treated cells, compared to butyrate or untreated cells. Finally, cells under all conditions expressed MAP2, a neural-specific microtubule associated protein. Together, these data suggest that intracellular cAMP levels modulate distinct subsets of the myogenic differentiation pathway in rhabdomyosarcoma cells. Moreover, they also indicate that RD cells are able to express markers of different cell lineages, which may help explain some of the paradoxical features of these tumors.
...
PMID:cAMP effects on myogenic gene expression in rhabdomyosarcoma cells. 880 51

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