RESUMEN
Receptor for hyaluronan-mediated motility (RHAMM) has previously been characterized as a cell surface receptor for hyaluronan and a microtubule-associated intracellular hyaluronan binding protein. We examined the expression of RHAMM mRNA in 43 oral squamous cell carcinomas (SCCs) and 7 normal gingivae by real-time RT-PCR. The expression level of RHAMM mRNA was significantly higher in oral SCCs than normal gingivae (P=0.0047). Forty out of 43 oral SCCs showed expression of RHAMM splice variant (48 bp deletion). We immunohistochemically confirmed the protein expression of RHAMM in oral SCCs with higher levels of RHAMM mRNA. Patients with oral SCC who had high RHAMM expression had shorter survival rates than patients with low expression. However, it was not statistically significant. It has been reported that RHAMM interacts with spindle assembly factors such as microtubule-associated protein (TPX2). To investigate the expression of microtubule-associated protein in oral SCCs, mRNA expression of TPX2 was also examined by real-time RT-PCR. The expression level of TPX2 mRNA was significantly higher in oral SCCs than normal gingivae (P=0.046). Furthermore, a significant correlation between the mRNA expression levels of TPX2 and RHAMM was recognized (P=0.011). The results indicate that there is a strong correlation between the mRNA expression levels of TPX2 and RHAMM in oral SCCs. Our observations suggest that the up-regulations of human RHAMM and TPX2 gene correlate with the malignant condition and might be linked to the increased or abnormal cell proliferation in human oral SCCs.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/genética , Proteínas de la Matriz Extracelular/genética , Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/genética , Proteínas Asociadas a Microtúbulos/genética , Neoplasias de la Boca/genética , Proteínas Nucleares/genética , Empalme Alternativo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Encía/metabolismo , Encía/patología , Humanos , Receptores de Hialuranos/metabolismo , Técnicas para Inmunoenzimas , Proteínas Asociadas a Microtúbulos/metabolismo , Neoplasias de la Boca/metabolismo , Proteínas Nucleares/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
TPX2 is a microtubule-associated protein and is required for microtubule formation at kinetochores in mammalian cells. The purpose of this study was to clarify the expression of TPX2 mRNA and correlation between TPX2 and clinicopathological factors in salivary gland carcinomas. The expression of TPX2 mRNA was investigated in 20 human salivary gland carcinomas (8 mucoepidermoid carcinomas, 7 adenoid cystic carcinomas, 5 acinic cell carcinomas) and 6 normal submandibular glands using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). The mean expression level of TPX2 mRNA was higher in mucoepidermoid carcinomas (0.53+/-0.51) than in normal submandibular glands (0.047+/-0.029); a significant association was found (Mann-Whitney U test, P=0.0067). The mean expression levels of TPX2 were also higher in acinic cell carcinomas (0.45+/-0.49) and adenoid cystic carcinomas (0.28+/-0.22) than in normal submandibular glands. Statistical correlations were found (Mann-Whitney U test, P=0.028 and P=0.003, respectively). Correlation between expression of TPX2 and receptor for hyaluronan-mediated motility (RHAMM) was also investigated in this study. A significant association was found between the mRNA expression levels of TPX and RHAMM (Pearson's correlation coefficient by rank test, P=0.020). These results indicate that human TPX2 mRNA is closely linked to increased or abnormal cell proliferation in malignant salivary gland tumors.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma/metabolismo , Proteínas de Ciclo Celular/biosíntesis , Proteínas Asociadas a Microtúbulos/biosíntesis , Proteínas Nucleares/biosíntesis , Neoplasias de las Glándulas Salivales/metabolismo , Carcinoma/patología , Proteínas de la Matriz Extracelular/biosíntesis , Expresión Génica , Humanos , Receptores de Hialuranos/biosíntesis , Inmunohistoquímica , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de las Glándulas Salivales/patologíaRESUMEN
We examined the expression of epiregulin and amphiregulin mRNA in 39 oral SCCs, 2 epithelial dysplasias and 7 normal gingivae by real-time RT-PCR. The mean expression level of epiregulin mRNA was higher in oral SCCs (0.29+/-0.50) than normal gingivae (0.01+/-0.007) and epithelial dysplasias (0.01+/-0.001). The expression level of epiregulin mRNA was significantly higher in oral SCCs than normal gingivae (Mann-Whitney U test, P=0.023). Epiregulin mRNA was higher in stage III/IV than in stage I/II oral SCCs. However, a significant association was not found. The mean expression level of amphiregulin mRNA was higher in oral SCCs (0.18+/-0.24) than normal gingivae (0.002+/-0.003) and epithelial dysplasias (0.01+/-0.001). Amphiregulin mRNA was significantly higher in oral SCCs than normal gingivae (Mann-Whitney U test, P=0.001). We then examined the expression of four EGF receptor mRNA in oral SCCs. The expression levels of HER1, HER2, HER3 and HER4 mRNA in oral oral SCCs were increased compared to those in normal gingivae. A significant correlation was found between the mRNA expression levels of epiregulin and HER2, HER3 and HER4 (Spearman's correlation coefficient by rank test, P=0.031, P=0.004 and P=0.027, respectively). Patients with oral SCC that have a high expression of epiregulin had a significantly shorter survival than those with low a expression (log-rank test, P<0.05). These results indicate that human epiregulin is closely linked to the increased or abnormal cell proliferation in human oral SCC.