Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three clonal rat rhabdomyosarcoma subpopulations (A, B, C) with a block of differentiation at different levels of rhabdomyogenesis were exposed to the differentiation inducers retinoic acid (RA), N-methylformamide (NMF) and sodium butyrate (NaBut). Since an increased expression of c-raf and c-fos had recently been demonstrated for subpopulation C after exposure to RA and NMF (1), the mRNA expression of c-raf, c-fos and retinoic acid receptor (RAR) alpha, beta and gamma was compared in all three subpopulations. After exposure to RA, NMF or NaBut, subpopulation C exhibited a significant (p = 0.0001) increase in creatine kinase (CK) activity and in morphological differentiation. In subpopulation B, the response was confined to a significant (p = 0.0001) increase in creatine kinase activity, whereas subpopulation A proved to be differentiation-refractory. On the molecular level, a uniform increase in c-raf expression became evident in all three subpopulations after 6 to 12 hours, persisting at an elevated level throughout the observation period of 120 hours. In contrast, the pattern of c-fos expression observed after exposure to RA, NMF or NaBut was heterogeneous. Expression of RAR alpha and gamma was detected in all subpopulations, whereas RAR beta mRNA was not expressed. Summarizing our results, the uniform pattern of c-raf expression might suggest a participation of c-raf in differentiation signal transduction. Since the three subpopulations differ markedly in their degree of differentiation, the block of differentiation characteristic for each subpopulation supposedly becomes effective only after the action of the c-raf gene product.
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PMID:Increase in proto-oncogene raf expression precedes differentiation induction in different clonal rhabdomyosarcoma subpopulations. 131 93

Cell sublines were derived from Ni-induced rat rhabdomyosarcoma which differed in their degree of tumorigenicity. We compared the expression of protein kinase C isoforms alpha, beta, gamma and epsilon in three sublines developing tumors in syngeneic rats (Sy+) and in two sublines devoid of tumorigenicity in these animals (Sy-), with that of normal skeletal muscle. Northern and Western blotting experiments showed that PKC alpha was dramatically overexpressed in Sy- cells whereas it was underexpressed in Sy+ cells. Southern blot analysis provided evidence for a 3-fold increase of PKC alpha-related DNA fragments in Sy- cells. Steady-state levels of the PKC epsilon-related transcript were also markedly decreased in Sy+ cells. However, the expression of PKC beta-related RNA was increased in these cells. Our data support the concept that the differential expression of the PKC isoforms may play a critical role in determining the neoplastic phenotype.
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PMID:Tumorigenicity-associated expression of protein kinase C isoforms in rhabdomyosarcoma-derived cells. 159 8

A series of 15 rhabdomyosarcomas was examined by light microscopy, transmission electron microscopy, two-dimensional gel electrophoresis (2D-GE) and indirect immunofluorescence, the latter using monoclonal or affinity-purified polyclonal antibodies to desmin, vimentin, alpha-smooth muscle and alpha-sarcomeric (alpha-sr) actins. By light microscopy, the authors diagnosed 1 botrioid, 1 alveolar, and 7 embryonal rhabdomyosarcomas, 4 pleomorphic spindle cell sarcomas, and 2 spindle cell sarcomas, one nondistinct, the other with a hemangiopericytomatous pattern. By transmission electron microscopy, 13 neoplasms disclosed rhabdomyoblastic differentiation; the remaining 2, myogenic differentiation. By immunofluorescence microscopy, all neoplasms expressed vimentin and alpha-sr actin, 12 expressed, in addition, desmin, and 1 expressed alpha-smooth muscle actin. Among the 11 neoplasms studied by means of 2D-GE, 7 demonstrated an alpha-actin spot, while 4 showed only beta and gamma spots. One tumor disclosed, in addition to alpha, beta, and gamma spots, a spot with a molecular weight corresponding to actin, but more acidic than alpha-actins. This study demonstrates that alpha-sr actin antibody represents a valuable marker for the diagnosis of rhabdomyosarcoma, because it was present in all neoplasms, including the one negative for desmin. This antibody further allowed the recognition of pleomorphic variants and morphologically atypical forms of rhabdomyosarcomas. The presence of alpha-smooth muscle actin in 1 case of rhabdomyosarcoma suggests that this actin isoform may be expressed during skeletal muscle differentiation.
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PMID:Intermediate filament proteins and actin isoforms as markers for soft tissue tumor differentiation and origin. II. Rhabdomyosarcomas. 327 94

Enolase isozymes (alpha, beta and gamma enolases) in the extracts of pediatric tumors (neuroblastoma, ganglioneuroblastoma, rhabdomyosarcoma and Wilms' tumor) were determined by means of enzyme immunoassay systems. All tumor tissues examined contained alpha enolase at high levels (2070-19100 ng/mg protein). The beta and gamma enolases were present at high levels particularly in rhabdomyosarcoma (886 +/- 750 ng/mg protein) and (ganglio)neuroblastoma (2060 +/- 890 ng/mg protein), respectively. Immunohistochemical studies confirmed these results. Serum levels of these enolase isozymes were also determined in pediatric tumor patients. Before treatment, a serum sample from a patient with rhabdomyosarcoma contained a high level of beta enolase and serum samples from patients with (ganglio)neuroblastoma contained high levels of gamma enolase. However, the levels of serum beta and gamma enolases were low in patients with Wilms' tumor. The elevated level of beta or gamma enolase in serum from rhabdomyosarcoma or (ganglio)neuroblastoma patients was markedly decreased after adequate treatment (operation, chemotherapy or radiation). The results indicated that the enolase isozymes are useful marker antigens for differential diagnosis and therapeutic monitoring of neuroblastoma and rhabdomyosarcoma.
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PMID:Enolase isozymes as markers for differential diagnosis of neuroblastoma, rhabdomyosarcoma, and Wilms' tumor. 632 51

A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) system has been developed to calculate the level of expression of human retinoic acid receptors (hRAR) alpha, beta, and gamma. Starting from a single cDNA preparation, the system allows the measurement of the number of molecules of each mRNA receptor. This is made possible by a synthetic internal standard mRNA which is added in known concentrations at the beginning of the reaction. The system is tested in a rhabdomyosarcoma cell line (A-673) where we have measured the upregulation of beta and gamma receptor mRNAs following treatment with retinoic acid.
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PMID:An improved RT-PCR protocol for the quantitation of human retinoic acid receptor RNA. 751 Feb 46

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.
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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