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- Cui, H, et al.
(författare)
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Inactivation of H19, an imprinted and putative tumor repressor gene, is a preneoplastic event during Wilms' tumorigenesis
- 1997
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Ingår i: Cancer Research. ; 57:20, s. 4469-4473
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Tidskriftsartikel (refereegranskat)abstract
- Genetic evidence shows that the parent of origin-dependent expression patterns of the Igf2 and H19 genes is coordinated in mouse, such that H19 controls the activity of Igf2 in cis. Equally compelling evidence for a similar situation in humans is absent, although the frequently observed activation of the maternal IGF2 allele (ie., loss of imprinting) in Wilms' tumors has been attributed to the silencing of the maternal H19 locus. We show here that loss of H19 activity is generally a preneoplastic event, which may be linked with an overgrowth lesion that has been proposed to be permissive for tumor formation. Although our results document one instance in which a postneoplastic loss of H19 activity correlates with loss of IGF2 imprinting at the cellular level, it appears that inactivation of H19 is more generally independent of loss of imprinting of IGF2, at least in our specimens. Our results imply that inactivation of H19 correlates with blastema overgrowth and can be independent of a regulatory role with respect to IGF2 imprinting status in cis.
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| 5. |
- Ohlsson, R, et al.
(författare)
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Random monoallelic expression of the imprinted IGF2 and H19 genes in the absence of discriminative parental marks
- 1999
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Ingår i: Dev Genes and Evolution. ; 209, s. 113-
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Tidskriftsartikel (refereegranskat)abstract
- PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated embryonic blood vessels and reduced numbers of both pericytes and trophoblasts. These changes are seen from embryonic day (E) 13.5, which coincides with the upregulation of PDGFB mRNA levels in normal placentas. By E17, modifications in shape, size, and number of the fetal blood vessels in the mutant placentas cause an abnormal ratio of the surface areas between the fetal and the maternal blood vessels in the labyrinthine layer. Our data suggest that PDGFB acts locally to contribute to the development of the labyrinthine layer of the fetal placenta and the formation of a proper nutrient-waste exchange system during fetal development. We point out that the roles of PDGFB/Rbeta signaling in the placenta may be analogous to those in the developing kidney, by controlling pericytes in the labyrinthine layer and mesangial cells in the kidney.
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| 8. |
- KANDURI, C, et al.
(författare)
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GENES WITHOUT PROTEIN PRODUCTS : IS H19 THE NORM OR THE EXCEPTION?
- 1999
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Ingår i: Current science. - 0011-3891. ; 77:4, s. 539-544
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- The increasing number of RNA polymease II transcripts without any apparent open reading frame has increased our awareness that gene functions can be selected for without involving a protein product.By using the H19 gene as a point of reference, we highlight here several common features among non-coding genes, such as their antisense position in subchromosomal expression domains which are often genomically imprinted. We also discuss the need to critically examine the translatability of transcripts which are considered non-coding. Finally, we present a model to explain the origin of non-coding genes.
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