RESUMEN
The complex insulin-like growth factor network of ligands, receptors and binding proteins has been shown to be disturbed in breast cancer. In addition to defects in proteins controlling cell cycle checkpoints, this type of aberrations could affect tumor growth and survival thereby influencing both tumor aggressiveness and potential response to treatments. We have previously identified the T1A12/mac25 protein, which is identical to the IGFBP-rP1, as a differentially expressed gene product in breast cancer cells compared with normal cells. Here we compare the expression of IGFBP-rP1 in 106 tumor samples with known status of cell cycle aberrations and other clinicopathological data. This was done using a tumor tissue section array system that allows for simultaneous immunohistochemical staining of all samples in parallel. Cytoplasmic staining of variable intensity was observed in most tumors, 15% lacked IGFBP-rP1 staining completely, 20% had weak staining, 32% intermediate and 33% showed strong staining. Low IGFBP-rP1 was associated with high cyclin E protein content, retinoblastoma protein (pRb) inactivation, low bcl-2 protein, poorly differentiated tumors and higher stage. There was a significantly impaired prognosis for patients with low IGFBP-rP1 protein tumors. Interestingly, IGFBP-rP1 showed an inverse association with proliferation (Ki-67%) in estrogen receptor negative tumors as well as in cyclin E high tumors suggesting a separate cell cycle regulatory function for IGFBP-rP1 independent of interaction with the estrogen receptor or the pRb pathway.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas Portadoras/análisis , Proteínas Portadoras/genética , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Aneuploidia , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Ciclo Celular/genética , Ciclo Celular/fisiología , Ciclina D1/análisis , Ciclina E/análisis , Diploidia , Femenino , Genes bcl-2 , Genes erbB-2 , Genes p53 , Humanos , Inmunohistoquímica , Metástasis Linfática , Menopausia , Invasividad Neoplásica , Estadificación de Neoplasias , Polimorfismo Conformacional Retorcido-Simple , Pronóstico , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Proteína de Retinoblastoma/metabolismo , Telomerasa/análisis , Proteína p53 Supresora de Tumor/análisisRESUMEN
The carbon-14 distribution in the abyssal waters of the world oceans indicates replacement times for Pacific, Indian, and Atlantic ocean deep waters (more than 1500 meters deep) of approximately 510, 250, and 275 years, respectively. The deep waters of the entire world ocean are replaced on average every 500 years.