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

In a search for novel transcriptional intermediary factors for the estrogen receptor (ER), we used the ligand-binding domain and hinge region of ER as bait in a yeast two-hybrid screen of a cDNA library derived from tamoxifen-resistant MCF-7 human breast tumors from an in vivo athymic nude mouse model. Here we report the isolation and characterization of the forkhead homologue in rhabdomyosarcoma (FKHR), a recently described member of the hepatocyte nuclear factor 3/forkhead homeotic gene family, as a nuclear hormone receptor (NR) intermediary protein. FKHR interacts with both steroid and nonsteroid NRs, although the effect of ligand on this interaction varies by receptor type. The interaction of FKHR with ER is enhanced by estrogen, whereas its interaction with thyroid hormone receptor and retinoic acid receptor is ligand-independent. In addition, FKHR differentially regulates the transactivation mediated by different NRs. Transient transfection of FKHR into mammalian cells dramatically represses transcription mediated by the ER, glucocorticoid receptor, and progesterone receptor. In contrast, FKHR stimulates rather than represses retinoic acid receptor- and thyroid hormone receptor-mediated transactivation. Most intriguingly, overexpression of FKHR dramatically inhibits the proliferation of ER-dependent MCF-7 breast cancer cells. Therefore, FKHR represents a bifunctional NR intermediary protein that can act as either a coactivator or corepressor, depending on the receptor type.
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PMID:Forkhead homologue in rhabdomyosarcoma functions as a bifunctional nuclear receptor-interacting protein with both coactivator and corepressor functions. 1135 74