Antiproliferative effect of Aurora kinase targeting in mesothelioma.
The Aurora proteins are a small family of serine/threonine kinase that function in various stages of mitosis. Current interest in Aurora kinase relates to its role in tumours, and its potential as a therapeutic target. In this work we studied the expression of Aurora kinases A and B and related genes in human mesothelioma tissues and in five mesothelioma cell lines. Moreover, we analyzed the effects of ZM447439 (ZM), an Aurora kinase inhibitor, on cellular growth. Results evidenced an over-expression of Aurora kinase A and related genes in human mesothelioma tissues and an over-expression of Aurora kinases A and B in all cell lines. Moreover, we demonstrated that ZM447439 was able to inhibit cell growth in all cell lines and that this inhibition was due to a specific effect as demonstrated by the reduction in the level of Histone H3 phosphorylation. Our findings support a role of Aurora kinase in mesothelioma and the possibility of using Aurora kinase inhibitors in therapeutic modalities.
Crispi
Stefania
S
Gene Expression Core-Human Molecular Genetics Laboratory, Institute of Genetics and Biophysics, CNR, Naples, Italy.
Fagliarone
Claudia
C
Biroccio
Annamaria
A
D'Angelo
Carmen
C
Galati
Rossella
R
Sacchi
Ada
A
Vincenzi
Bruno
B
Baldi
Alfonso
A
Verdina
Alessandra
A
D064096:Aurora Kinase A; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D046228:Microarray Analysis; D010766:Phosphorylation / Q000187:drug effects; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology
C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D001549:Benzamides; D006657:Histones; D011799:Quinazolines; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases