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 the clonal human rhabdomyosarcoma cell line TE-671-1A, the expression of genes implicated in myogenic differentiation was determined before and after exposure to the differentiation inducers retinoic acid (RA), sodium butyrate (NaBut) and N-monomethylformamide (NMF). Exposure to NaBut or RA resulted in a significant (NaBut: p < 0.0001; RA: p < 0.05) increase in biochemical differentiation paralleled by a significant (NaBut: p < 0.0001; RA: p < 0.0002) inhibition of proliferation. An increase in the relative number of myotube-like giant cells was observed after exposure to NaBut. Exposure to NMF proved to be least effective and produced a significant (p < 0.0001) inhibition of proliferation without increase in differentiation. On the molecular level, exposure to RA resulted in a moderate increase in RAR a mRNA expression, whereas CRABP mRNA remained constant. RAR beta and RAR gamma mRNA were not expressed. mRNA expression of c-raf, c-myc and c-Ki-ras remained constant before and after exposure to all inducers of differentiation. C-fos mRNA was not expressed. In summary, differentiation can successfully be induced in the human rhabdomyosarcoma cell line TE-671-1A by various inducers of differentiation. In contrast to other myogenic cell lines, however, the proto-oncogenes myc, fos and raf are not involved in the transmission of myogenic differentiation signals in TE-671-1A cells.
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PMID:Differentiation induction in the human rhabdomyosarcoma cell line TE-671. A morphological, biochemical and molecular analysis. 773 31

The ability of retinoids to induce growth inhibition associated with differentiation of diverse cell types makes them potent anti-cancer agents. We examined the effect of retinoic acid (RA) in cell lines derived from rhabdomyosarcoma (RMS), a malignant soft-tissue tumor committed to the myogenic lineage, but arrested prior to terminal differentiation. We showed that several RMS derived cell lines, including RD human rhabdomyosarcoma cells, are resistant to the growth-inhibitory and differentiation effects of RA. We established that this RA-resistance correlates with reduced expression and activity of RA-receptors in RD cells. We stably expressed either RARalpha, RARbeta, RARgamma, or RXRalpha expression vector into RD cells and found that only RARbeta or RARgamma induced a significant RA growth arrest without promoting differentiation indicating that changes in the amounts of RARs and RXRs are not sufficient to determine the RA myogenic response of rhabdomyosarcoma cells. Activation of RD cell differentiation by ectopic MRF4 expression enhanced RA-receptor activity and led to RA induction of differentiation. These studies demonstrate that RA-resistance of RD cells is linked to their lack of differentiation and suggest that the differentiation-promoting activity of RA requires factors other than RAR-RXR heterodimers.
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PMID:Response of human rhabdomyosarcoma cell lines to retinoic acid: relationship with induction of differentiation and retinoic acid sensitivity. 1623 81

Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is composed of 855 amino acids, contains 15 tetratricopeptide repeat motifs, and associates with Cockayne syndrome group A and B proteins and RNA polymerase II, as well as XPA. In vitro and in vivo studies showed that XAB2 is involved in pre-mRNA splicing, transcription, and transcription-coupled DNA repair, leading to preimplantation lethality, and is essential for mouse embryogenesis. Retinoids are effective for the treatment of preneoplastic diseases including xeroderma pigmentosum and other dermatologic diseases such as photoaging. We therefore focused on defining the effect of XAB2 on cellular differentiation in the presence of ATRA treatment. In the present study, we showed that overexpression of XAB2 inhibited ATRA-induced cellular differentiation in human rhabdomyosarcoma cell line, and that knockdown of XAB2 by small interfering RNA (siRNA) increased ATRA-sensitive cellular differentiation in the human promyelocytic leukemia cell line HL60 at both physiologic (10(-9)-10(-8) mol/L) and therapeutic (10(-7) mol/L) concentrations of ATRA. Moreover, we found that XAB2 was associated with retinoic acid receptor alpha (RARalpha) and histone deacetylase 3 in the nuclei. Finally, using siRNA against XAB2, we showed that the ATRA-resistant neuroblastoma cell line IMR-32 underwent cellular differentiation induced by ATRA at a therapeutic concentration (10(-6) mol/L). These results strongly suggest that XAB2 is a component of the RAR corepressor complex with an inhibitory effect on ATRA-induced cellular differentiation and that XAB2 plays a role in ATRA-mediated cellular differentiation as an important aspect of cancer therapy.
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PMID:Knockdown of XAB2 enhances all-trans retinoic acid-induced cellular differentiation in all-trans retinoic acid-sensitive and -resistant cancer cells. 1728 34