Dominant-negative inhibition of Ets 1 suppresses tumor growth, invasion and migration in rat C6 glioma cells and reveals differentially expressed Ets 1 target genes.

We previously reported that the inactivation of the Ets 1 transcription factor by a specific decoy strategy reduces rat C6 glioma cell proliferation and mmp-9 expression. In the present study, we analysed the effects of the dominant-negative form of Ets 1 (Ets-DB) on rat C6 glioma cell proliferation, migration, invasion, in vivo tumor growth on the chicken chorioallantoic membrane (CAM) and mmp-9 expression. In addition, we examined differences in gene expression between Ets-DB expressing and control cells using suppression subtractive hybridization (SSH).

Myc confers androgen-independent prostate cancer cell growth.

Prostate cancer is one of the most diagnosed and mortal cancers in western countries. A major clinical problem is the development of androgen-independent prostate cancer (AIPC) during antihormonal treatment. The molecular mechanisms underlying the change from androgen dependence to independence of these tumors are poorly understood and represent a challenge to develop new therapies.

Expression of an Ets-1 dominant-negative mutant perturbs normal and tumor angiogenesis in a mouse ear model.

We and others have shown that members of the Ets family of transcription factors are involved in morphogenic properties of endothelial cells in vitro. To investigate the role of these factors in the transcriptional regulation of angiogenesis in vivo, we set up a nontraumatic model that allows daily macroscopic examination of both growth factor- and tumor-induced angiogenesis in mouse ears. In the same animal, we were thus able to record variations in the patterns of neovessels induced and cell populations recruited by the angiogenic factors FGF-2 and VEGF.

[Experimental angiogenesis : strategy for the functional study of the transcription factors of the Ets family during morphogenesis of the vascular tree].

During morphogenesis of the vascular tree, the massive outgrowth of primitive capillaries is followed by the development and the maturation of some capillary branches whereas others regress. The direct observation and the manipulation of in vivo models, including a series of recent knock-out experiments, allow to delineate the mechanisms controlling this process, and to identify factors involved in the formation of a mature capillary, surrounded with a basal lamina and pericytes. The expression of several members of the Ets family of transcription factors, Ets1, Erg and Fli, correlates with the occurrence of invasive processes, such as angiogenesis during normal and pathological development.

Multidrug resistance protein-mediated transport of chlorambucil and melphalan conjugated to glutathione.

The human multidrug resistance protein (MRP1) confers resistance of cells to a number of different cytostatic drugs and functions as an export pump for glutathione S-conjugates, glucuronides and other amphiphilic anions. The present study details for the first time MRP1-mediated ATP-dependent transport of various glutathione S-conjugates of the bifunctional alkylating agents chlorambucil and melphalan. In membrane vesicles prepared from cells expressing recombinant MRP1, the conjugates were transported at rates in the following order: monoglutathionyl chlorambucil > bisglutathionyl chlorambucil > monohydroxy monoglutathionyl chlorambucil and monoglutathionyl melphalan > monohydroxy monoglutathionyl melphalan.