On the other hand consistent pattern of phosphorylation was not witnessed in melanoma cell lines Our stu dies are in line with recent findings which indicate that in neoplastic cells, the action of signalling pathways won’t constantly correlate with all the mutational standing of upstream proteins mainly in the MAPK pathway This heterogeneity in signalling phenotype is constant with the large degree of variability during the patterns of gene expression observed in these melanoma cell lines Previous scientific studies have shown that PIK3CA mutations can result in hyperactivated PI3K signalling pathways Having said that, this phenomenon was not continually observed in all NZM cell lines studied Our success are similar to that of Morrows et al. who observed unique patterns of signalling in colon tumour cell lines harbouring the identical mutation.
They are also consistent with scientific studies by other groups in the variety of non melanoma cell lines A degree of plexity is supplied by the effects of the latest examine of MCF seven cells by which each of the sublines designed from the parental MCF seven cell line had been all anticipated buy MLN8237 to get precisely the same PIK3CA mutation, but not each of the sub lines showed strong PKB phosphorylation. The outcomes suggest that to some extent the signalling phenotype may be independent of genotype. All NRAS only mutant cell lines showed serum inde pendent phosphorylation of ERK1 two regardless of no observa ble phosphorylation of MEK1 two The outcomes are surprising but are constant together with the observation of Pratilas et al. who found that ERK phosphorylation was not indicative of signalling with the MEK path way, as ERK phosphorylation can be regulated by nega tive suggestions loops. In addition, ERK1 2 is phosphorylated despite tiny MEK1 two phosphorylation in some NZM cell lines, suggesting MEK independent reg ulation of ERK.
It has inhibitor SCH66336 been advised that PI3K and classical protein kinase C play a serious role from the MEK independent prolonged activation of ERK in some cell forms As every one of the NZM cell lines utilized in this review are mutant for either BRAF or NRAS, this suggests that these oncogenic mutations confer activa tion of the MAPK pathway. Nevertheless, the dominant sig nalling pattern observed in all the NZM cell lines is serum independent phosphorylation of ERK1 2 pared to melanocytes. We also didn’t observe NZM cell lines lacking PTEN perform to get strongly asso ciated with inactivation of MEK1 2 and ERK1 2 inside the MAPK pathway as mentioned by Dan et al. A attainable explanation for this is that all the NZM cell lines studied for functional PTEN loss also have BRAF mutations. Despite the fact that Dan et al. suggests that muta tions in both NRAS or BRAF are strongly correlated with PI3K PKB pathway inactivation, we didn’t observe this in the panel of NZM cell lines. A further result of this review is that, from the presence of serum, the phosphorylation pattern of usual melanocytes is usually much like that of melanoma cells, distinctions are additional plainly seen when the cell lines are grown during the absence of serum.