The results show that tumor sizes were closely dependent on numbers of R2N1d cells initially inoculated, cells inoculated. These tumors were processed for immunohistochemical study. Histological sections of the resected tumor revealed sheets of cells Ruxolitinib with Inhibitors,Modulators,Libraries nuclear enlargement, high nucleocyto plasmic ratio, hyperchromasia and pleiomorphism. There were areas where tumor cells invaded neighboring tissue. These tumor cells showed the expres sion of Ki 67, VEGF, COX 2 and MMP 9 that are known to be expressed in inva sive and metastatic tumors. These results clearly show that R2N1d cells with HER2 overexpression were highly tumorigenic, whereas R2d cells were non tumorigenic. High frequency of R2N1d cells expressed breast cancer stem cell markers Since cancer stem cells initiate and sustain tumor growth, these cells are also considered as targets for cancer ther apy.
For breast cancer, CD44 CD24 /low and alde hyde dehydrogenase have been reported as markers for breast cancer stem cells. We examined the expression of CD44 CD24 /low in R2d and R2N1d cells by flow cytometric analysis. The results Inhibitors,Modulators,Libraries revealed a very high frequency of CD44 CD24 /low cells in R2N1d cells compared to that in R2d cells. It is also noted that a subpopulation of CD44high cells appeared in R2N1d cell culture. The results of this study clearly show that a major function of HER2 is to increase the frequency of CD44 high/CD24 cancer stem cells. Non adherent R2N1d cells Inhibitors,Modulators,Libraries derived from adherent monolayer culture lost HER2 and CD44 CD24 expression CD44 CD24 cells were sorted out from R2N1d cells by flow cytometry.
These cells tend to show contact insensitive growth in monolayer and gave rise to non adherent Inhibitors,Modulators,Libraries cells in suspension in extended growth. Experiments were carried out to compare gene expres sion of adherent and non adherent R2N1d cells as well as reattached non adherent cells after replating. By flow cytometric analysis and by western blotting, the results indicate that, while Oct 4 expressions were comparable in the 3 different populations of cells, the HER2 expres sion was significantly reduced in non adherent cells. After incubation of non adherent R2N1d Inhibitors,Modulators,Libraries cells for 3 weeks, a few of these suspended cells re attached and proliferated. These re attached cells were found to express HER2 and Oct 4 similar to their parental adher ent cells.
Results presented previously show that HER2 and PI3K/Akt activity regulate the selleck chemical expression HDAC6. Consistent with this function, we found that adherent and reattached R2N1d cells expressed HER2 as well as AKT1 and HDAC6, whereas non adherent R2N1d cells in suspension lost the expression of these 3 markers. The expression of CD44 CD24 in non adherent R2N1d cells was found to be dramati cally reduced compared to adherent cells, reaffirming the regulation of CD44 CD24 expression by HER2.
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