C-Jun and Cyclin D1 Proteins as Mediators of Neuronal Death after a Focal Ischaemic Insult.

International audienceC-JUN, a transcriptional activator, as well as cyclin D1, a key regulator of the cell cycle, have been described in vitro as mediators of programmed neuronal death. After trophic factor deprivation, the activation of c-jun and cyclin D1 genes is considered as a necessary step within the cellular machinery that leads to cell death. We show here that both c-Jun and cyclin D1 proteins are present in neurones within the infarcted area after experimental cerebral ischaemia in the mouse. Since their presence was associated with DNA fragmentation revealed by the TUNEL procedure, we propose that c-Jun and cyclin D1 are involved in the process of neuronal death

Overexpression of cyclin D2 in chronic B-cell malignancies

Tumor progression in B-cell chronic lymphocytic leukemia (B-CLL) is thought to result from the gradual accumulation of small resting G0/G1 phase lymphoid cells rather than the proliferation of actively dividing cells. The recent identification of G1 cyclins that are likely to control both the progression through G0 and G1 phase and the G1/S transition prompted us to study the mRNA expression of D-type cyclins in the peripheral blood lymphocytes from 34 patients with B-CLL, 7 patients with lymphoplasmacytic lymphoma (LPL), and 2 patients with mantle cell lymphoma (MCL). Cyclin D2 mRNA was, on average, 5- to 10-fold overexpressed in most of the samples studied (B-CLL, 29/34; LPL, 7/7; MCL, 0/2) as compared with normal resting B lymphocytes, in which cyclin D2 mRNA was barely detectable. In situ hybridization with cyclin D2 digoxigenin-labeled mRNA probe showed that all the cells from a given sample were stained with approximately the same intensity. Cyclin D3 was never detected in any of the samples tested, whereas cyclin D1 was expressed in only the 3 cases (1 LPL and 2 MCL) bearing a t(11;14) translocation. A trisomy 12 was found in 4 of 19 (21%) B-CLL or LPL cases for which cytogenetic analysis was available. Although the cyclin D2 gene has been mapped to chromosome 12p13, there was no apparent correlation between trisomy 12 and the level of cyclin D2 expression. Cell cycle analysis by flow cytometry after staining with propidium iodide consistently showed that more than 96% of the cells were in G0/G1 phase, whatever the importance of cyclin D2 overexpression was, and that cyclin D2 overexpression in B-CLL was not associated with any modifications of the cell cycle repartition. No consistent overexpression of cyclin D2 was found in acute myeloid leukemias. In conclusion, overexpression of cyclin D2 mRNA was found to be an almost constant feature in B-CLL and LPL. Therefore, it led us to hypothesize, with the support of data from some transfection experiments previously reported in murine hematopoietic cell lines, that cyclin D2 might play a role in B-CLL pathogenesis, possibly by preventing cells from programmed cell death.</jats:p