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Our laboratory has previously shown that apelin is mitogenic for endothelial cells. We have postulated that apelin represents an angiogenic factor secreted by tumour cells in order to promote the formation of new vessels necessary for tumour growth. We first demonstrate that apelin and its receptor are not expressed by the mouse TS/A mammary carcinoma cells. We therefore established clones of this tumoral cell type stably overexpressing the apelin cDNA (TS/A-apelin clones). Comparison of the in vitro proliferation rates between TS/A-mock and TS/A-apelin cells did not reveal any difference and confirmed the lack of receptor expression by tumour cells. On the other hand, apelin overexpression clearly increased the in vivo tumour growth and this increase was associated with an earlier onset of tumour development. In tumours derived from TS/A-apelin clones, the expression of the endothelial marker CD31 was increased and revealed the formation of large intratumoral vessels lined with CD31 positive cells. These data suggest that apelin behaves as a potent activator of tumour neoangiogenesis by a paracrine effect on host vessels. The pathological relevance of this finding is demonstrated by hypoxia-induced upregulation of apelin gene and its overexpression in one-third of human tumours.Oncogene (2007) 26, 7692–7699; doi:10.1038/sj.onc.1210573; published online 11 June 2007 [ABSTRACT FROM AUTHOR]

In embryonic cell-line derivative KCo of Drosophila melanogaster, the nucleolus, like most nucleoli, contains a small proportion of ribosomal DNA (1-2% of the total nucleolar DNA). The ribosomal DNA is virtually the only active gene set in the nucleolus and is found among long stretches of inactive supercoiled heterochromatic segments. We have demonstrated by use of a Feulgen-like ammine-osmium staining procedure that, depending on the state of growth, more or less fibres of decondensed DNA emanating from the intra-nucleolar chromatin (which is in continuity with the nucleolus-associated chromatin) ramify and unravel within the central nucleolar core to be transcribed. The nucleolus expands or contracts with the variation of activity and could belong to a supramolecular matricial structure such as is shown after extraction of the nuclei. After a long period of exposure to high doses of actinomycin D, the central nucleolar core became an homogeneous fibrous structure that could be interpreted as an aggregate of protein skeletal elements. The mechanism of repression and derepression of the nucleolar chromatin could thus be explained by a mechanism involving in part a sub-nucleolar structure. We propose a schematic organization of the nucleolar chromatin in KCo cells of Drosophila and discuss it in relation with other nucleolar organizations. [ABSTRACT FROM AUTHOR]

In mouse oocyte during meiotic prophase I, rRNA synthesis increases from midpachytene (onset of nucleologenesis) to the diplotene stage (both 4C DNA containing). During these stages the nucleoli undergone morphological changes from the ring-shaped structure to the nucleolonemal type. The results we obtained by 3-D reconstruction after serial sectionning of different nuclei during these stages, showed that there is an increase in the number of fibrillar centers (from 5-7 to 97-113) in correlation with the development of the nucleolonema. This result demonstrated that the fibrillar centers cannot be considered only as the interphasic counterparts of the nucleolar organizers in reticulated nucleoli. By a quantitative ultrastructural analysis of the respective volumes of fibrillar centers and other nucleolar components after serial sectionning we demonstrated that in oocyte nuclei and in mouse sertoli cell nuclei 1. there is a correlation between the number of fibrillar centers and their total volume, and 2. there is a relationship between the volume of fibrillar centers and the volume of the electronopaque fibrillar zone of the nucleolus, in which rDNA transcription occurs. This result, thus, demonstrated that the number and volume of the fibrillar centers are correlated, at least in reticulated nucleoli, with the activity of the nucleolar organizers. The more active the nucleolus, the more numerous the fibrillar centers and the larger their total volume. [ABSTRACT FROM AUTHOR]