RESUMO
BACKGROUND: The PI3K/AKT/mTOR pathway is central to prostate cancer progression. A preliminary investigation of immuno-histochemical expression of mammalian target of rapamycin (mTOR) pathway markers was undertaken to identify patterns of expression in prostate tissue. METHODS: Immunohistochemistry was performed on a custom-made prostate tissue array. Mean long scores and variability of long scores for each marker were recorded for normal lumenal cells, prostate intraepithelial neoplasia (PIN), and cancer. RESULTS: Expression of PTEN decreased and mTOR signaling pathway markers increased in PIN and in cancer as compared to normal cells in the majority of samples. Overexpression of 4E-BP1 and p-4E-BP1 was observed in PIN and cancer. However, in cancer, the overexpression of 4E-BP1 was significantly higher than with any other marker. DISCUSSION: Results suggest that 4E-BP1 overexpression is strongly associated with prostate cancer, especially when combined with PTEN and mTOR expression data. Hierarchical clustering analysis utilizing PTEN, mTOR, and 4E-BP1 separated normal from cancer cell populations in most cases.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/análise , Biomarcadores Tumorais/análise , PTEN Fosfo-Hidrolase/análise , Fosfoproteínas/análise , Neoplasias da Próstata/química , Proteínas Quinases/metabolismo , Transdução de Sinais , Proteínas de Ciclo Celular , Humanos , Imuno-Histoquímica , Masculino , Estadiamento de Neoplasias , Próstata/química , Próstata/patologia , Neoplasia Prostática Intraepitelial/química , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/patologia , Proteínas Quinases/análise , Serina-Treonina Quinases TORRESUMO
Aurora-2 is a serine threonine kinase that associates with the centrosome. Overexpression or ectopic expression of Aurora-2 appears to alter centrosome number and function and has been implicated in a variety of human cancers. In this work, we demonstrate that Aurora-2 is both amplified and overexpressed in human pancreatic cancer cell lines, with a 2-5-fold increase in gene copy number and a 3-4-fold increase in protein levels compared with controls. Aurora-2 is also amplified and overexpressed in pancreatic cancers taken directly from patients. An immunohistochemistry of tissues taken directly from patients demonstrated an overexpression of Aurora-2 in 26 of 28 pancreatic cancers compared with 18 normal pancreas samples. Antisense nucleotides specifically targeted at Aurora-2 arrest the cell cycle in pancreatic cancer cells, indicating the potential of Aurora-2 as a therapeutic target in pancreatic cancer.
