title: Lentiviral-mediated gene silencing of Notch-4 inhibits in vitro proliferation and perineural invasion of ACC-M cells.
abstract: Salivary adenoid cystic carcinoma (SACC) is a common type of salivary gland cancer. The poor long-term prognosis for patients with SACC is mainly due to local recurrence, perineural invasion (PNI) and distant metastasis. Notch signaling plays a critical role in determining cell fate such as proliferation, differentiation and apoptosis. Accumulating evidence indicates that aberrant Notch-4 expression has a tumor-promoting function in SACC. In the present study, we used lentiviral-mediated RNA interference (RNAi) targeted against Notch-4 to determine the effects of decreased levels of this protein in the human highly metastatic adenoid cystic carcinoma cell line ACC-M. Furthermore, the proliferative capability as well as the PNI potential of the treated cells were observed in vitro. Our studies demonstrated that RNAi directed against Notch-4 markedly decreased Notch-4 gene expression, resulting in the inhibition of cell proliferation, and G0/G1 to S phase arrest in ACC-M cells. Knockdown of Notch-4 also resulted in a decrease in the in vitro PNI activity in ACC-M cells. To conclude, RNAi targeting against Notch-4 induces the suppression of cell growth and inhibition of PNI in vitro in ACC-M cells. Notch-4 may play an important role in regulating proliferation and PNI activity of SACC.
authors: Department of Stomatology, Nanjing Jinling Hospital, Nanjing University, School of Medicine, Nanjing, Jiangsu, PR China.
authors: Wei
authors: W
authors: Chen
authors: Huali
authors: H
authors: Zhang
authors: Jiandong
authors: J
authors: Wang
authors: Gang
authors: G
authors: Cao
authors: Zhen
authors: Z
authors: Dong
authors: Han
authors: H
authors: Su
authors: Xiaojun
authors: X
authors: Zhou
authors: Senlin
authors: S
authors: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics*; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch