RESUMEN

LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Epitelial de Ovario/metabolismo , Proteínas del Citoesqueleto/metabolismo , Proteínas con Dominio LIM/metabolismo , Neoplasias Ováricas/metabolismo , Receptor ErbB-2/metabolismo , Transducción de Señal/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Epitelial de Ovario/patología , Línea Celular Tumoral , Estudios de Cohortes , Proteínas del Citoesqueleto/genética , Femenino , Células HEK293 , Humanos , Proteínas con Dominio LIM/genética , Lapatinib/farmacología , Persona de Mediana Edad , Neoplasias Ováricas/patología , Fosforilación/efectos de los fármacos , Fosforilación/genética , Plásmidos , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Receptor ErbB-2/genética , Transducción de Señal/efectos de los fármacos , Transfección