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)

In three cases of alveolar rhabdomyosarcoma with variant translocations, two tumors contained an identical translocation, t(1;13)(p36.1;q14); the third tumor contained a t(8;13)(p21;q14). All three patients were 2 years old, markedly younger than the median age for patients with t(2;13)-positive alveolar rhabdomyosarcoma. The alteration of genetic material on chromosome 13 may be of primary importance in the development of alveolar rhabdomyosarcoma.
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PMID:Variant translocations of chromosome 13 in alveolar rhabdomyosarcoma. 177 15

The effect of the activated c-Ha-ras oncogene on invasiveness and formation of spontaneous metastases was studied using the rhabdomyosarcoma R1H of the rat. R1H tumor cells which are able to grow in vitro and produce tumors upon subcutaneous injection in syngeneic WAG/Rij rats were transfected with the c-Ha-ras (EJ) oncogene and the neomycin gene for selection. Two R1H cell lines harboring and expressing the human c-Ha-ras oncogene, one cell line containing the neomycin gene only, and the parent R1H cell line were compared. The expression of the transfected c-Ha-ras oncogene was assessed by Northern blot analysis and by flow cytometry using antibodies against ras p21. No difference in tumor growth rate and morphology was observed for the transfected and untransfected cell lines. Tumor volume doubling time was about 2 days in R1H-ras as well as in R1H parent tumors. Formation of spontaneous metastases was tested by excising the tumors when they had reached a volume of 2 cm3; after that the animals were observed up to 12 months. The excised tumors still contained and expressed the transfected ras oncogene as proved by Southern blot analysis and antibody staining using anti-ras p21. In contrast to most previous work on ras-transfected tumorigenic cells the R1H-ras tumors did not acquire invasive growth potential or increased metastatic capacity.
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PMID:No acquisition of metastatic capacity of R1H rhabdomyosarcoma upon transfection with c-Ha-ras oncogene. 219 92

The cell line TE671 has been widely used as a model of human medulloblastoma. In the present study we have demonstrated that transfection of DNA from this cell line into NIH 3T3 cells reveals the presence of an activated N-ras gene. Using oligonucleotide probes we have shown that the N-ras gene is activated by a point mutation at the third base of codon 61 resulting in the substitution of histidine for glutamine in the p21 ras gene product. We noted that this relatively uncommon activating mutation is also present in the human rhabdomyosarcoma cell line RD. Based on this finding and on the observation that several of the phenotypic characteristics of TE671, such as the presence of muscle-type nicotinic acetylcholine receptors and the intermediate filament protein desmin, are suggestive of myoid origin we investigated the possible identity of these two cell lines. Cytogenetic analysis revealed the presence of marker chromosomes common to both TE671 and RD. DNA fingerprinting using both locus specific and multilocus core probes showed indistinguishable band patterns in the two cell lines. Taken together our data show that TE671 and RD are derivatives of the same cell line and we conclude that the properties of the TE671 line should be ascribed to rhabdomyosarcoma rather than medulloblastoma cells.
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PMID:Characterization of the human cell line TE671. 265 Sep 8

In the cytogenetic analysis of an embryonal rhabdomyosarcoma after short-term culture, individual cells were found to contain multiple copies of chromosomes #2, #6, #8, #12, #13, #18, #20 and #21, and del(1)(:p21----qter). The tumor was hypotriploid (mode, 56 chromosomes). The relationship between these findings and published reports of karyotypes from rhabdomyosarcoma is discussed.
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PMID:A cytogenetic study of embryonal rhabdomyosarcoma. 396 22

The basic helix-loop-helix protein MyoD induces muscle structural gene expression and cell cycle withdrawal in many nontransformed cell lines. We show that MyoD activation of transcription of the cyclin-dependent kinase inhibitor p21 does not require synthesis of an intermediary protein. In most of the rhabdomyosarcoma and other solid tumor cell lines that we analyzed, p21 levels were abnormally low and correlated with the combined inactivity of MyoD and p53, two known transcriptional activators of p21. Loss of MyoD activation of p21 transcription correlated with the failure to arrest in G1, and expression of p21 caused accumulation of cells in G1, further supporting a role for p21 in MyoD-induced cell cycle arrest. Finally, different tumor types have inactivated distinct factors necessary for p21 expression, because p21 expression was reconstituted in hybrid cell lines. We propose that p21 integrates growth-inhibitory signals from independent p53 and basic helix-loop-helix pathways, and that in the majority of tumor cell lines, both pathways are abrogated.
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PMID:Inactivation of MyoD-mediated expression of p21 in tumor cell lines. 937 38

High levels of insulin-like growth factor II (IGFII) mRNA expression are detected in many human tumors of different origins including rhabdomyosarcoma, a tumor of skeletal muscle origin. To investigate the role of IGFII in tumorigenesis, we have compared the mouse myoblast cell line C2C12-2.7, which was stably transfected with human IGFII cDNA and expressed high and constant amounts of IGFII, to a control cell line C2C12-1.1. A rhabdomyosarcoma cell line, RH30, which expresses high levels of IGFII and contains mutated p53, was also used in these studies. IGFII overexpression in mouse myoblast C2C12 cells causes a reduced cycling time and higher growth rate. After gamma-irradiation treatment, C2C12-1.1 cells were arrested mainly in G0/G1 phase. However, C2C12-2.7 and RH30 cells went through a very short G1 phase and then were arrested in an extended G2/M phase. To verify further the effect of IGFII on the cell cycle, we developed a Chinese hamster ovary (CHO) cell line with tetracycline-controlled IGFII expression. We found that CHO cells with high expression of IGFII have a shortened cycling time and a diminished G1 checkpoint after treatment with methylmethane sulfonate (MMS), a DNA base-damaging agent, when compared with CHO cells with very low IGFII expression. It was also found that IGFII overexpression in C2C12 cells was associated with increases in cyclin D1, p21, and p53 protein levels, as well as mitogen-activated protein kinase activity. These studies suggest that IGFII overexpression shortens cell cycling time and diminishes the G1 checkpoint after DNA damage despite an intact p53/p21 induction. In addition, IGFII overexpression is also associated with multiple changes in the levels and activities of cell cycle regulatory components following gamma-irradiation. Taken together, these changes may contribute to the high growth rate and genetic alterations that occur during tumorigenesis.
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PMID:Diminished G1 checkpoint after gamma-irradiation and altered cell cycle regulation by insulin-like growth factor II overexpression. 1022 65

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.
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PMID:Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia. 1037 68

The relationship between G(1) checkpoint function and rapamycininduced apoptosis was examined using two human rhabdomyosarcoma cell lines, Rh1 and Rh30, that express mutated p53 alleles. Serum-starved tumor cells became apoptotic when exposed to rapamycin, but were completely protected by expression of a rapamycin-resistant mutant mTOR. Exposure to rapamycin (100 ng/ml) for 24 h significantly increased the proportion of Rh1 and Rh30 cells in G(1) phase, although there were no significant changes in expression of cyclins D1, E, or A in drug-treated cells. To determine whether apoptosis was associated with continued slow progression through G(1) to S phase, cells were exposed to rapamycin for 24 h, then labeled with bromodeoxyuridine (BrdUrd). Histochemical analysis showed that >90% of cells with morphological signs of apoptosis had incorporated BRDURD: To determine whether restoration of G(1) arrest could protect cells from rapamycin-induced apoptosis, cells were infected with replication-defective adenovirus expressing either p53 or p21(CIP1). Infection of Rh30 cells with either Ad-p53 or Ad-p21, but not control virus (Ad-beta-gal), induced G(1) accumulation, up-regulation of p21(CIP1), and complete protection of cells from rapamycin-induced apoptosis. Within 24 h of infection of Rh1 cells with Ad-p21, expression of cyclin A was reduced by >90%. Similar results were obtained after Ad-p53 infection of Rh30 cells. Consistent with these data, incorporation of [(3)H]thymidine or BrdUrd into DNA was significantly inhibited, as was cyclin-dependent kinase 2 activity. These data indicate that rapamycin-induced apoptosis in tumor cells is a consequence of continued G(1) progression during mTOR inhibition and that arresting cells in G(1) phase, by overexpression of p53 or p21(CIP1), protects against apoptosis. The response to rapamycin was next examined in wild-type or murine embryo fibroblasts nullizygous for p53or p21(CIP1). Under serum-free conditions, rapamycin-treated wild-type MEFs showed no increase in apoptosis compared to controls. In contrast, rapamycin significantly induced apoptosis in cells deficient in p53 ( approximately 2.4-fold) or p21(CIP1) ( approximately 5.5-fold). Infection of p53(-/-) MEFs with Ad-p53 or Ad-p21 completely protected against rapamycin-induced apoptosis. Under serum-containing conditions, rapamycin inhibited incorporation of BrdUrd significantly more in wild-type murine embryo fibroblasts (MEFs) than in those lacking p53 or p21(CIP1). When BrdUrd was added 24 h after rapamycin, almost 90% and 70% of cells lacking p53 or p21(CIP1), respectively, incorporated nucleoside. In contrast, only 19% of wild-type cells incorporated BrdUrd in the presence of rapamycin. Western blot analysis of cyclin levels showed that rapamycin had little effect on levels of cyclins D1 or E in any MEF strain. However, cyclin A was reduced to very low levels by rapamycin in wild-type cells, but remained high in cells lacking p53 or p21(CIP1). Taken together, the data suggest that p53 cooperates in enforcing G(1) cell cycle arrest, leading to a cytostatic response to rapamycin. In contrast, in tumor cells, or MEFs, having deficient p53 function the response to this agent may be cell cycle progression and apoptosis.
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PMID:p53/p21(CIP1) cooperate in enforcing rapamycin-induced G(1) arrest and determine the cellular response to rapamycin. 1130 95

Rhabdomyosarcoma (RMS) cell lines were transduced with an adenoviral vector containing the wild-type p53 (wtp53) cDNA (Ad-p53) and then exposed to four cytotoxic agents: actinomycin D, vincristine, 5-fluorouracil and bleomycin. Potentiation of cytotoxicity following wild-type p53 expression varied from 0- to 20-fold for different drugs and between cell lines. It appeared that alveolar RMS cells (n = 2) were more susceptible to p53-mediated chemosensitization than embryonal RMS cells (n = 3), although this was independent of pax3-FKHR expression. Overall, cells that were most chemosensitive prior to Ad-p53 exposure were those that were most susceptible to p53 potentiation of cytotoxicity. The different results obtained with these RMS cell lines does not appear to be related to expression of pax3-FKHR, p21, Bax or Bcl-2 but may in part be due to differential regulation of p53 target genes, such as MDM2. In conclusion, exogenous wild-type expression selectively chemosensitizes RMS cells to cytotoxic agents. However, expression of transcriptionally active wtp53 does not predict a chemosensitive phenotype.
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PMID:Selective chemosensitization of rhabdomyosarcoma cell lines following wild-type p53 adenoviral transduction. 1239 75

In this study, we investigated the mRNA level of several genes involved in cell cycle regulation in alveolar (ARMS) and embryonal rhabdomyosarcomas (ERMS). p21(Cip1), Cyclin D1, Cyclin D2, Cyclin D3, CDK2, and CDK4 were evaluated by RT-PCR. All (13 out of 13) ERMS expressed the p21(Cip1) gene compared with only 40% (4 out of 10) of the ARMS. Moreover, the amount of p21(Cip1) mRNA was noticeably higher in the ERMS samples than in the positive ARMS specimens. p27(Kip1) protein were analysed by immunohistochemical and immunoblotting. A noticeable difference was observed, in that ERMS had higher amounts of the cell cycle inhibitor compared with the ARMS. Finally, treatment of two rhabdomyosarcoma cell lines, RH-30 and RD, with butyrate, resulted in complete growth inhibition and in the upregulation of the p21(Cip1) and p27(Kip1) levels. Our results demonstrate that ERMS have a much higher level of p27(Kip1) and p21(Cip1) than the alveolar types, explaining, at least in part, the distinct features and outcomes (i.e. a poor prognosis of the alveolar type) of the two forms of this childhood solid cancer. Moreover, the data on butyrate-treated cell lines suggest that the two genes are potential novel therapeutic targets for the treatment of rhabdomyosarcomas.
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PMID:Cell division cycle control in embryonal and alveolar rhabdomyosarcomas. 1244 Dec 66


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