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

We created pCOL-KT, a plasmid construct in which the promoter/enhancer of human Pro alpha 1(I) gene is linked to the chloramphenicol acetyl transferase reporter gene. The Pro alpha 1(I) promoter/enhancer in pCOL-KT was methylated in vitro and tested for transcriptional activity by transient expression analysis. Methylation of the construct with bacterial methylases reduced transcriptional activity about 25-fold. Site-specific methylation of eight potential canonical sites of eukaryotic methylation within the promoter greatly reduced transcriptional activity. Chromatin conformation of the transfected pCOL-KT DNA was analyzed by nuclease sensitivity. Although both methylated and unmethylated transfected DNA had increased susceptibility to DNase I compared with the endogenous gene, the methylated transfected DNA showed increased resistance to nuclease when compared with unmethylated transfected DNA, indicating that the methylation of the DNA alters the chromatin conformation. We also tested the ability of a human rhabdomyosarcoma cell line that does not express type I collagen to support transcription from an exogenously added Pro alpha 1(I) promoter/enhancer. The transformed cell line is able to support transcription from the Pro alpha 1(I) promoter/enhancer. Treatment of the transformed cell line with 5-azacytidine, a potent inhibitor of DNA methylation, resulted in transcriptional activation of the Pro alpha 1(I) gene. These findings, along with the extreme methylation sensitivity of the Pro alpha 1(I) promoter and enhancer, suggest that DNA methylation may be an important mechanism of transcriptional inactivation of interstitial collagen genes.
 ...
PMID:In vitro methylation of the promoter and enhancer of Pro alpha 1(I) collagen gene leads to its transcriptional inactivation. 199 5

Collagens are a heterogeneous family of structural proteins synthesized by many cultured cells including tumor cells. The synthesis of these proteins by three human tumor types commonly encountered in children [neuroblastoma, rhabdomyosarcoma, and nephroblastoma (Wilms' tumor)] was investigated in short-term cultures of freshly excised tumor explants grown on extracellular matrices. Analysis of the incorporation of [3H]proline into collagenase-sensitive proteins indicated significant collagen production by several Wilms' tumors and rhabdomyosarcomas, while neuroblastomas did not synthesize this structural protein. All eight Wilms' tumor specimens analyzed secreted type IV procollagen. Interstitial types I and III collagens were also produced by these tumors, but in most cases, the alpha 1 (I): alpha 2 ratio was much higher than the 2:1 ratio expected for type I collagen, indicating a major change in the control of type I collagen production. Rhabdomyosarcomas were very heterogeneous with regard to collagen secretion and synthesized either a single collagen isotype (type III), several collagens including types I, III, and IV, or no detectable collagen. Our data represent a first quantitative and qualitative analysis of collagen synthesis by primary tumor cultures and reveal much more heterogeneity in collagen biosynthesis by these tumors than reported previously with established cell lines. They also indicate significant alterations in the expression of type I collagen genes in Wilms' tumors.
 ...
PMID:Collagen synthesis by short-term explants of pediatric tumors. 298 85