We then examined the effect of abrogation of E-cadherin function on the activity of the EGFR/ERK and PI3-K/AKT pathways.
This work elegantly and systematically describes the effect of abrogation of the gamma secretase component Aph1B in synaptic transmission, plasticity, and dendritic spine formation, and provides convincing data pointing towards the neuregulin 1 intracellular domain as a downstream regulator of these events.
Next, the in vivo effects of combined abrogation of JAK2 activity by TG101209 and Bcl-2/Bcl-xL by ABT-737 were assessed.
Next, we addressed the effect of Trf1 abrogation in immortalization of MEFs.
The above data prompted us to investigate the effect of the abrogation of CCR9 on murine CIA.
The role of p53-family members in the transcriptional regulation of NIS expression was further confirmed by the strong effect of the abrogation of p53, p63 and p73 expression by specific siRNAs (Supplementary Figure S3) on NIS promoter activity.
Using one such cell line, K1, we have tested the effect of experimental abrogation of p53 function by generating matched sub-clones stably expressing either a neo control gene, a dominant-negative mutant p53 (143ala) or human papilloma virus protein HPV16 E6.
To assess the effect of Trf1 abrogation in the context of lung cancer induced by expression of the K-Ras G12V oncogene, we crossed K-Ras+ /LSLG12Vgeo mice (designated from now on as K-Ras+ /G12V ) (Guerra et al, 2003) to a strain carrying a floxable allele of Trf1 (Trf1 lox/lox ) either wild-type or deficient for p53 (p53−/−) (Martinez et al, 2009) (Fig. 1A).
In aggregate, these data further confirmed with functional application that the increases observed in E-cadherin, α-and β-catenins, and p120 levels in Cetrorelix-exposed DU-145 WT cells are the results of a reversal of the cells invasive phenotype to one that resembles a more normal phenotype and that Cetrorelix exerts at least some of its effects via abrogation of autocrine EGFR cell signalling.
Importantly, these studies led to identify that the chemical inhibition of Rap-1 reproduces the effects of JAM-A abrogation, thus opening the possibility of developing specific drugs to improve stem cell engraftment.
