erbB2 gene silencing and its effect on PTEN in SACC-83 salivary adenoid cystic carcinoma cells

Abstract

Abstract. erbB2 gene plays an important role in carcinoma formation. erbB2 overexpression was observed in many types of tumours, including salivary carcinoma. However, a putative erbB2 and PTEN interaction remains largely unknown in salivary adenoid cystic carcinoma cells. The purpose of this study was to silence erbB2 gene and investigate the functional relationship between erbB2 and PTEN in SACC-83 salivary adenoid cystic carcinoma cells. erbB2-specific siRNAs were transfected into SACC-83 cells using cationic liposome. RT-PCR, immunocytochemistry and Western blotting were employed to detect erbB2 and PTEN expression. Compared with the control groups, erbB2 mRNA expression was decreased in the erbB2-siRNA transfection group, and immunocytochemistry and Western blotting indicated a concordant erbB2 protein reduction. The average optical density values for erbB2 proteins in erbB2-siRNA transfected group were significantly lower than that in the control groups (P<0.05). On the other hand, PTEN expression at both mRNA and protein levels were not significantly affected by erbB2 silencing (P>0.05). In conclusion, the data indicate that siRNA could effectively silence erbB2 gene expression in SACC-83 cells, but PTEN expression appeared unaltered following erbB2 silencing. PTEN expression might not be strictly associated with erbB2 amplification in SACC-83 cells. Future studies will more closely examine the molecular and biological relationships of erbB2 and PTEN in salivary adenoid cystic carcinoma. IntroductionSalivary adenoid cystic carcinoma (SACC) is a common oral tumour, known to be highly destructive and unpredictable (1-3). Previous research has demonstrated a possible role of oncogenic activation in SACC (4-6). erbB2, also called HER2, is a cell surface receptor tyrosine kinase (RTK) and becomes internalized upon ligand binding which can trigger a multitude of signaling pathways, such as MAPKs and PI3K. The erbB family consists of four structurally related tyrosine kinase receptors: erbB1, erbB2, erbB3, and erbB4. These four receptors contain multiple cytosolic tyrosines, which can interact with one or more adaptor proteins to activate downstream signaling pathways when phosphorylated. Furthermore, the erbB receptors display functional redundancy with overlapping signaling pathways. erbB2 is the preferred heterodimerization partner of all erbB proteins, and plays important roles in the lateral transmission of signals between other erbB receptors (7). Consequently, erbB2 has been shown to trigger signal transduction leading to cell growth and differentiation. Tumours showing erbB2 amplification/ overexpression have been shown to demonstrate increased aggressiveness and metastatic potential and decreased overall survival (8-10). In previous studies, erbB2 gene expression was found to be elevated in many types of tumours, including salivary gland carcinoma (11-13).PTEN is an important tumour suppressor gene located on chromosome 10q23.3. The encoded protein displays homology with the catalytic domain of tyrosine...

Bioinformatic Analysis for Mucoepidermoid and Adenoid Cystic Carcinoma of Therapeutic Targets

“…HER2 (erbB-2/neu) is a tyrosine kinase that activates MAPK and PI3K pathways to cell growth and differentiation. In tumors, it is possible to observe gene amplification or overexpression that could be related to more aggressive and metastatic behavior, decreasing the survival expectation of a patient with many carcinomas, including AdCC [37].…”