You don't go from normal liver to liver cancer overnight but what you do go through is a process from our normal liver with fibrosis to sue roses to regenerative psoriasis modules with the cells are obviously proliferating within an orderly fashion constrained by surrounding fibrous tissue are that can go on to develop a low grade and then subsequently high-grade plasticity changes and then finally our progress in too early for pedophile carcinoma the morphology changes associated with this a really difficult to our report on pathologist and it's a you it's a your.

I think Philly fine distinction arm but are one that apologists can agree on so what people have shown in focusing particular that during this progression there are accumulating genetic and epigenetic modifications to the soul that actually lead an account for the malignant transformation and in particular a par a genome-wide screen as well as arm intensive use love all the nucleotide microarrays applied to considerable number of cancers love divers ideologies suggests that in this transition from.

The high-grade dysplasia Nigel to the early the cellular proto-oncogene thematic place they really fundamentally important role in that pathway analysis suggests that in over 85 percent of those tumors during this progression there inactivation over seem control pathway as reflected in the diagram top so that actually correlates with increasing see make copy number without duplication of the eight cue chromosomal region in the cells and suggests that see make plays a central role in the development of liver cancer of multiple etiologies not just have to see that's no repercussions they don't.

I'm not going to talk too much more about that however I if you a few expressed seem Eric in a transgenic mouse model these mice far developed liver cancer and arm if you look also in those mice you'll see that in the parasites with the third bar here misses again work from stories where both published in Gastroenterology last year there is both increased proliferation other parasites as indicated by PCNA labeling arm are in the issue and also increased paper posters for parasites so us see Mick over expression in the liver promotes Palace on a proliferation also promotes pedal cycle death now other work from stories lab indicates that over expression I V to have which is a another cellular proto-oncogene.

It's transcription factor that regulated by the retinoblastoma gene we'll come back to that in just a minute also causes liver cancer in mind in it also causes increased arm proliferation and increased a pop poses as well but what's important is that there is an interaction betweene2f in cement in that e2f expression in double knockout alpha shred double transgenic excuse me reduces the apotheosis that you see cause by seem Eric over expression so if you look then at what appears to be cooperative actions a thematic any 2f both so you're proto-oncogene both love the song to James driver so to proliferate not shown the pathways over here on the right largely through emptor and increased cellular translation but.