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ompared to vehicle treated cells,Accordingly, BMP4 also significantly decreased the size of the acini structures as evidenced by a 40% オーダー KU-0063794 reduction in the total area covered by the cell clusters at day 14,In PEG gel, vehicle treated MCF 10A cells mainly formed round cell clusters with occasional protrusions whereas BMP4 treated cells formed irregularly shaped elongated structures with high numbers of protrusions,In addition, BMP4 inhibited the proliferation of the MCF 10A cells by 69% at day 11 as compared to the vehicle,Analysis of the area covered by cells revealed a maximum reduction of 51% at day 7 after BMP4 treatment,BMP4 induces different phenotypes in breast cancer cells in 3D Next we examined the effects of BMP4 in 3D cultures of four breast cancer cell lines.<br><br>@@ The cell lines were chosen based on our previous data showing a prominent phenotype upon BMP4 stimulation in 2D,either G1 cell cycle arrest and growth inhibition and or increased migration,T 47D cells formed irregular raft like structures in Matrigel,BMP4 treatment did オーダー Lenalidomide not induce any obvious changes in the morphology of the cell clusters but inhibited cell proliferation,The size of the area covered by cells was similarly reduced by 43% and 39% at days 7 and 10, respectively,At day 14 the difference was 28% but just failed to reach statistical significance,In PEG gel, the T 47D cell structures were either round or polygonal in shape, in both BMP4 and vehicle treated samples,BMP4 induced a distinct decrease in cell proliferation at days 11 and 14,Consequently, there was a significant reduction in the size of the cell area, ranging from 64% at day 7 to 79% at day 14,For BT 474 cells, the consequences of BMP4 treatment were first examined in 2D culture due to lack of previous information.<br><br>@ A significant decrease in cell count was detected in BMP4 treated cells as LY294002 154447-36-6 compared to vehicle,In Matrigel the cells formed dense, mostly round structures,Proliferation was reduced by 26% already at day 7 and continued to decrease up to 36% at day 14 after BMP4 treatment,A concomitant reduction of 40% to 50% on average could be seen in the area measurements,MDA MB 361 cells grew very slowly in both 3D envi ronments and therefore were allowed to grow up to 18 days,In Matrigel, the cells formed small mostly round masses, and BMP4 treatment induced no consistent changes in prolifera tion, area or morphology of the cells,In contrast, in PEG gel BMP4 significantly decreased proliferation at day 11 through day 18,In addition, BMP4 de creased the size of the area covered by cells, with a max imum reduction of 48% at day 11,However, no changes in the morph ology of the cell structures were observed in PEG gel with both BMP4 and vehicle treatments resulting in round cell clusters.<br><br>@ MDA MB 231 cells formed mostly dense and compact round or oval structures in Matrigel with occasional branches,Interestingly, BMP4 had a major impact on the morphology of the cells.<br><br> It induced the formation of large branching stellate structures, which extended over large areas of the gel,The first evidence on this effect was seen already at day 7, but it became prominent after 10 days in culture,On the other hand, BMP4 did not have an effect on the proliferation of the MDA MB 231 cells as measured by alamarBlue or the area covered by the cells,It should be noted that the latter result is hindered by the difficulties in accurately measuring the area of the BMP4 induced stellate structures.@ In PEG gel, no branching was observed and the MDA MB 231 cell masses were typically round or irregularly shaped in both BMP4 and vehicle treated samples,Interestingly, BMP4 significantly inhibited proliferation of the MDA MB 231 cells in PEG gel, with a 36% reduc tion by day 14,Similarly, the area covered by the cells was diminished by a maximum of 36% at day 11,BMP4 induced growth arrest is partly explained by induction of p21 expression We have previously shown that the growth inhibition caused by BMP4 in breast cancer cell lines growing in monolayer culture is due to a G1 cell cycle arrest,To investigate this further, the effect of BMP4 on the ex pression of 11 known cell cycle regulators was measured in T 47D and MDA MB 361 cells grown for 24 hours in 2D.<br><br>@ A change in the expression of the cell cycle inhibitor p21, phosphorylated CDC2 and Cyclins B1 and B2 was seen in both cell lines, with at least a 2 fold difference in one of the cell lines,Among these, induction of p21 was the most prominent and was thus selected for further evaluation. We verified that p21 expression was also induced by BMP4 in 2D culture of MDA MB 231 and BT 474 cells,In MCF 10A cells, distinct p21 induction was evident only after a prolonged BMP4 treatment and was accompanied by a G1 cell cycle arrest,In Matrigel, the p21 levels were determined at day 4 or 7 after BMP4 treatment.@ BMP4 had no effect on p21 expression in MCF 10A cells whereas it did induce p21 expression in T 47D, BT 474, MDA MB 361 and MDA MB 231 cells,Induction o