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)

The role of phosphatidylinositol 3-kinase and FK506-binding protein rapamycin-associated protein (FRAP) in translational control has been examined by treating RD-rhabdomyosarcoma cells with wortmannin and rapamycin and studying the effects on cell-growth, translation initiation, and protein synthesis. Whereas wortmannin and rapamycin exhibit subtle effects on global translation, examination of individual mRNAs in sucrose gradients and of individual proteins in two-dimensional polyacrylamide gels reveals that wortmannin and rapamycin exhibit distinct effects on the translation of individual mRNAs. Wortmannin represses the synthesis of a third of cellular proteins, whereas rapamycin affects a subset of these proteins. Since ribosomal protein S6 was rapidly dephosphorylated following wortmannin and rapamycin treatment, and the phosphorylation status of the eukaryotic initiation factor 4E was unchanged, our data imply that the p70 signalling pathway has at least one branch-point upstream of FRAP leading to an additional route of translational control.
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PMID:Distinct repression of translation by wortmannin and rapamycin. 924 59

Insulin-like growth factors (IGFs) can stimulate skeletal muscle differentiation. One of the molecular mechanisms underlying IGF-stimulated myogenesis is transcriptional induction of myogenin. The current work is aimed to elucidate the signaling pathways mediating the IGF effect on myogenin promoter in mouse C2C12 myogenic cells. We show that phosphatidylinositol 3-kinase (PI3K)/Akt and p70(S6K) are crucial signaling molecules mediating the stimulatory effect of IGFs on myogenin expression. We have identified three cis-elements, namely the E box, MEF2, and MEF3 sites, within the 133-base pair mouse proximal myogenin promoter that are under the control of the IGF/PI3K/Akt pathway. Simultaneous mutation of all three elements completely abolishes activation of the myogenin promoter by PI3K/Akt. We demonstrate that PI3K/Akt can increase both the MyoD and the MEF2-dependent reporter activity by enhancing the transcriptional activity of MyoD and MEF2. Interestingly, IGF1 does not enhance myogenin expression in Rhabdomyosarcoma-derived RD cells. Consistently, the constitutively active PI3K/Akt fail to activate the myogenic reporters, suggesting the IGF/PI3K/Akt pathway is defective in RD cells and the defect(s) is downstream to PI3K/Akt. This is the first time that a defect in the IGF/PI3K/Akt pathway has been revealed in RD cells which provides another clue to future therapeutic treatment of Rhabdomyosarcoma.
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PMID:The insulin-like growth factor-phosphatidylinositol 3-kinase-Akt signaling pathway regulates myogenin expression in normal myogenic cells but not in rhabdomyosarcoma-derived RD cells. 1097 62

Insulin-like growth factor (IGF-II) is overexpressed in a variety of human tumors and has both mitogenic and antiapoptotic activity. Although the mechanisms of IGF-II-induced proliferation have been well studied, the mechanisms underlying its survival signaling have been less well characterized. In this report, we investigated the role of IGF-II on cisplatin-induced apoptosis. We found that IGF-II overexpression was associated with an increase in p70 ribosomal protein S6 kinase (p70 S6K). Cisplatin treatment of C2C12 mouse myoblasts led to cell death associated with an inhibition of p70 S6K activity. Endogenous or exogenous IGF-II addition to C2C12 cells caused protection to cisplatin-induced apoptosis. This protection was associated in both cases with an increase in p70 S6K basal activity as well as resistance to cisplatin-induced decreased activity. Blockade of p70 S6K activation by rapamycin abrogated the IGF-II-mediated protection of cells to cisplatin-induced apoptosis. Furthermore, treatment of IGF-II-overexpressing Rh30 and CTR rhabdomyosarcoma cells with rapamycin restored sensitivity to cisplatin-induced apoptosis. These data together suggest that IGF-II-associated protection to cisplatin-induced apoptosis is mediated through an activation of the p70 S6K pathway. Thus, inhibition of the p70 S6 pathway may enhance chemotherapy-induced apoptosis in the treatment of IGF-II-overexpressing tumors.
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PMID:Effect of insulin-like growth factor II on protecting myoblast cells against cisplatin-induced apoptosis through p70 S6 kinase pathway. 1219 98