Thus, other factors are required to sustain cycling of multipolar mitotic esophageal cancer cells in order to allow development and maintenance of individual aneu ploid ESCC and BAC cell clones. Since up to 80% of ESCC and 90% of BAC display mutations of p53, this molecular weight calculator tumor suppressor protein is a very likely contributing factor, particularly in view of its role in G1 cell cycle and DNA damage control, its centrosomal function as well as its inactivation and or degra dation upon interaction with Aurora A. Thus, cells with still intact or only partial dysfunctional p53 protein may still have p53 dependent G1 cell cycle con trol, a scenario that was of interest for the present data, particularly for the ESCC Kyse 410 cells.

In the present study, p53 mutations were found in the four representative esophageal cancer cell lines, but in different domains and therefore with different conse quences for protein expression and or function. None of the p53 mutations detected corresponded to known p53 gain of function mutations. Instead, OE21 cells had p53 mutations, which caused weak expression of a presum ably non functional, largely truncated p53 protein. Also OE33 cells had a p53 mutation resulting in a non functional, nuclear accumulated p53 protein, lacking transactivation and growth suppressive activity. In contrast, Kyse 410 cells had a cell culture acquired p53 mutation, resulting in expression and nuclear accumulation of an at least par tially functional p53 protein. Similarly, the p53 mutation confirmed in OE19 cells , may cause expression of a truncated, but still partially func tional p53 protein with lost oligomerization activity.

Thus, esophageal cancer cells with both high Aurora A expression and p53 loss of function mutations have a high occurrence of multipolar mitoses. In contrast, esophageal cancer cells with Aurora A gene amplification and high Aur ora A expression, but an at least partially functional p53 protein have fewer multipolar mitoses. In contrast to the esophageal cancer cells, the normal esophageal epithelial cell line EPC hTERT was diploid, had wild type p53 and did show normal Aur ora A and Aurora B gene copy numbers as well as bipo lar mitoses. Still, slightly elevated Aurora A and p53 protein levels were observed in this cell line. Although no effect of hTERT was seen on p16 and p53 protein levels in the initial description of this Carfilzomib cell line, others have reported an effect of hTERT induced down regulation of p16, p21 and up regulation of Aurora A in normal esophageal epithelial cells, which may explain the detectable Aurora A protein expression observed in our experiments of EPC hTERT cells.