RESUMEN
Sprouty2 is known for its tumor-suppressing effect in various human malignant diseases. In head and neck squamous cell carcinoma (HNSCC), the role of sprouty2 in tumorigenesis and clinical implication remains elusive. The aim of the present study was to investigate the expression of sprouty2 in patients with HNSCC and its function in vitro. Quantitative analysis of mRNA expression of sprouty2 was performed on frozen tumor samples from 42 patients with HNSCC and 19 with oral verrucous hyperplasia (OVH) with paired counterparts of normal mucosa. Downregulation of sprouty2 expression was demonstrated in 79% of HNSCC samples and in 58% of OVH samples compared with paired samples of normal mucosa. Enhanced expression of sprouty2 protein suppressed the growth of HNSCC cells and signaling of the phosphorylated AKT pathway. Following transfection of the sprouty2 plasmid, HNSCC cells were more sensitive to sorafenib, a tyrosine kinase inhibitor of Raf and vascular endothelial growth factor receptor. The present study suggested that sprouty2 expression was downregulated and behaved as a tumor suppressor in HNSCC. Sprouty2 expression in tumor cells enhanced sensitivity to sorafenib. Further studies are required to define the clinical impact of sprouty2 in patients with HNSCC.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Resistencia a Antineoplásicos/genética , Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Hiperplasia , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Clasificación del Tumor , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Niacinamida/análogos & derivados , Niacinamida/farmacología , Fosfohidrolasa PTEN/metabolismo , Compuestos de Fenilurea/farmacología , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sorafenib , Carcinoma de Células Escamosas de Cabeza y Cuello , Carga TumoralRESUMEN
The oral tyrosine kinase inhibitors of epidermal growth factor, erlotinib and gefitinib, are active in the treatment of non-small cell lung cancer (NSCLC). However, a number of skin manifestations have been found in patients receiving erlotinib therapy. Leukocytoclastic vasculitis is a rare side-effect of erlotinib therapy. However, whether or not erlotinib treatment should be continued when disseminated ulceration of leukocytoclastic vasculitis is encountered remains to be determined. In this study, we report a patient with NSCLC who remains responsive to erlotinib treatment following successful rechallenge with a reduced dose of erlonitib after presenting with severe degree of leukoclastic vasculitis.
RESUMEN
Sprouty2 (Spry2) was identified recently as a tumor suppressor gene in cancer cells which inhibits the activation of receptor tyrosine kinases (RTKs). The present study explored the effect of Spry2 in colon cancer cells in order to assess its potential use in the treatment of colon cancer. Expression of Spry2 inhibited the growth of a colon cancer cell line, HCT116, and induced sensitization to fluorouracil (5-FU) and metformin. Spry2 promoted apoptosis of cancer cells in association with activation of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) pathway and the blockade of Ras-Raf-Erk signaling. Treatment of Spry2-HCT116 cells with metformin resulted in a more prominent effect on the inhibition of cell migration. Inhibition of microRNA-21 (mir21) induced upregulation of Spry2 and PTEN which underscores the importance of mir-21 in Spry2-associated tumorigenesis of the colon. These results point toward a potential strategy for colon cancer treatment worthy of further investigation.