lst cell cycle dynamics of esophageal cancer cells clearly selleckchem impact detection levels of Aurora A expression, additional regulation of Aur ora A expression by transcriptional, for example via epi dermal growth factor receptor, and post translational, for example via Inhibitors,Modulators,Libraries the ubiquitin proteasome pathway, mechanisms may further act in individual esophageal cancer cells. Indeed, the clinical relevance of Aurora A in esophageal cancers has mainly been deter mined at the expression level. In contrast to Aurora A, there was a more close asso ciation between Aurora B gene copy numbers and Aur ora B mRNA and protein expression in the ESCC and BAC cell lines. Both ESCC cell lines had elevated Aurora B gene copy numbers due to chro mosome 17 polysomy and concomitant high Aurora B expression, but not activation.

Instead, both BAC cell lines dis played lower Aurora B gene specific signals than chro mosome 17 specific signals with concomitantly low Aurora B mRNA as well as protein expression and activity. In fact, also our previous studies showed broad chromosomal deletions on 17p close to the Aurora B locus in up to 40% of tissue specimens of BACs, whilst other Inhibitors,Modulators,Libraries investigators reported Inhibitors,Modulators,Libraries controversial results for chromosome 17p alterations in tissue specimens of ESCC. In order to rule out that this is due to a major chromosome 17 alteration, we performed FISH and immunoblot analysis for HER2, clearly demonstrating that HER2 is highly amplified in these two BAC cell lines. This suggests that the detected genomic alteration is specific to 17p, respective poten tially the Aurora B gene.

The apparently reduced Aur ora B gene Inhibitors,Modulators,Libraries copy numbers in BAC cells may be due to a partial deletion, loss of the short arm of chromosome 17 or even duplication of centromere 17 alone. It will be of interest for future studies to investigate potentially deregulated chromosome integrity, for example by telo mere alterations or breakage fusion bridge cycles, during mitosis of BAC cells. Irrespective of this, the present results allow further insights into the direct association of high Aurora A expression with supernumerary centrosomes and the associated occurrence of multipolar mitoses and aneu ploidy described in other model systems now also for aneuploid esophageal cancer cells.

For example, ectopic overexpression of functional Aurora A in diploid colorectal cancer cell Drug_discovery line or ectopic expression of kinase deficient Aurora A isoforms, which is unable to phosphorylate its substrate Lats2, in immortalized fibro blasts both resulted in either supernumerary cen trosomes, chromosome segregation defects and or genomic instability. In fact, we found that high Aurora A expression in aneuploid ESCC or BAC cells does not excellent validation determine the occurrence of multipolar mitoses alone, 1 although exhibiting similarly high Aurora A expression, only OE33 cells, but not Kyse 410 cells were characterized by a high frequency of multipolar mitoses and 2 of the two cell lines with markedly lower Aurora A expression, OE21