EGFR expression has been shown to become regulated by a lot of factors that regulate growth and proliferation. In breast cancer, EGFR and ErbB2 expression was discovered to become below management from the Y box transcription translation element YB1 and that is phosphorylated by Akt. Nonetheless, YB1 has been shown to manage the two EGFR and ErbB2 expression. As we didn’t observe upregula tion of ErbB2 in our flotillin one knockdown cells, YB1 is not really quite prone to be the reason for EGFR upregulation upon flotillin 1 knockdown. Interestingly, earlier scientific studies have advised that ele vated flotillin two expression in gastric cancers correlates with ErbB2 amounts, and flotillins are needed to stabilize ErbB2 inside the plasma membrane in SKBR3 breast cancer cells.

Depletion of either of the flotillin proteins resulted in enhanced endocytosis and degradation of ErbB2 in from this source these cells, implicating that flotillins regulate ErbB2 trafficking. Additionally, flotillins were located to kind complexes with ErbB2, which also contained the heat shock protein Hsp90. However, this appears to not be the situation in MCF7 cells during which the amount of ErbB2 was not altered on flotillin depletion. Therefore, it’s evident that flotillins exhibit distinctive effects on receptor trafficking and signaling in breast cancer cells of various origin. That is not surprising, taking into consideration that the cell lines utilised are distinctive with regards to their genetic back ground and oncogenic mutations that are present in these cells. As an example, in accordance towards the Sanger institute COS MIC database, MCF7 cells exhibit a mutation within the catalytic subunit of PI3K, whereas SKBR3 cells have a WT PI3K.

Nonetheless, the two cell lines express non mutated EGFR and Ras proteins. A further aspect that might impact the outcomes obtained in several studies will be the usually means of knocking down flotil lin expression. For dig this example, Lin et al. described that flotillin 1 knockdown in MCF7 cells decreases cell viability and impairs tumorigenicity in MCF7 cells. In contrast to these data, we right here observed elevated MAPK signaling and increased cyclin D mRNA expression upon flotillin 1 ablation. Moreover, Lin et al. detected a decreased AKT phosphorylation and concomitant upregulation on the forkhead transcription issue Foxo3 and that is associ ated with decreased cell viability on account of upregulation of apoptotic genes. While Foxo3 expression was in creased in our flotillin one knockdown cells, we did not observe any evident impairment of AKT activation, in contrast to Lin et al.