Whether or not lack of Lats2 phosphorylation alone and or other selleck inhibitor alterations of the Aurora A isoforms, such as incorrect intracellular localization, are responsible for genomic instability in esophageal cancer cells remained elusive. In contrast, Aurora B is involved in kinetochore microtubule interactions, chromosome condensation and cytokinesis. Together with INCENP, survivin and borealin, Aurora B builds the chromosomal passen ger complex. The Aurora B gene is located in the chromosomal region 17p13. 1, which is also frequently altered in ESCCs and BACs. Although the role of Aurora B in human cancer is less clear than for Aurora A, an association between Aurora B overexpression and aneuploidy has been reported for some cancer cell lines.

However, in esophageal cancer the association of Aurora A and Aurora B with occurrence of multipolar mitoses in aneuploid ESCC or BAC cells remains elusive so far. In view of the crucial role of the tumor suppressor p53 for maintenance of genetic Drug_discovery stability and its frequent mutation in esophageal cancer, it is of interest that also a centrosomal localization and func tional involvement in centrosome duplication has been described for p53. Moreover, p53 can be phos phorylated by Aurora A, leading to MDM2 dependent p53 inactivation and degradation and or loss of p53 transactivation activity. Together, disruption of p53 function may result in escape of the p53 dependent G1 post mitotic checkpoint and potentially also centrosomal dysfunction.

The aim of the present study was to investigate the occurrence of multipolar mitoses and association with Aurora selleck chemicals Crenolanib kinases and p53 mutations in previously estab lished esophageal carcinoma cell lines and con trol esophageal epithelial cells. Results Ploidy and cell cycle distribution in normal esophageal epithelial cells and esophageal cancer cells For the present study, a control diploid cell line derived from normal esophageal epithelial cells as well as four aneuploid esophageal cancer cell lines with squa mous cell and adenocarcinoma differentiation and growth pat terns, i. e. closely reflecting the morphological features of the two main histotypes of esophageal can cer, were used. All experimental data shown are derived from each three independent experiments. Ploidy, respective DNA content, as well as cell cycle distribution patterns of all five cell lines was first defined by flow cytometry. This validated diploidy of EPC hTERT cells and aneuploidy to different levels in the esophageal cancer cell lines. To further define chromosome numbers in the aneuploid esopha geal cancer cell lines, each 10 metaphase spreads were analyzed and revealed highest chromosome numbers in OE33, followed by Kyse 410, OE21 and OE19 cells.