Double strand RNA-guided endogeneous E-cadherin up-regulation induces the apoptosis and inhibits proliferation of breast carcinoma cells in vitro and in vivo.
E-cadherin plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Down-regulation of E-cadherin expression correlates with a strong invasive potential, resulting in poor prognosis in many human carcinomas, including breast cancer. Restoration of E-cadherin can inhibit cell invasion and metastasis in many types of tumors. It has been demonstrated that promoter hypermethylation causes transcriptional down-regulation of E-cadherin. Here, using an RNAa technique specifically activating the expression of E-cadherin through transcriptional regulation, we assessed the phenotype changes of a breast carcinoma cell line with transfection of small-activating RNAs (saRNAs). We observed cell apoptosis, proliferation inhibition and reduction in human breast cancer migration in vitro. Animal experiment results showed that saRNA could inhibit tumor growth in vivo compared with scramble double-small RNA (dsRNA).This study provides a new potential strategy for breast cancer therapy, and also demonstrates the potential for saRNA as a therapeutic option for enhancing tumor suppressor gene expression in breast cancer. (Cancer Sci 2010).
Junxia
Wei
W
Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Ping
Gao
G
Yuan
Han
H
Lijun
Zhang
Z
Jihong
Ren
R
Fang
Lin
L
Min
Long
L
Xi
Wang
W
Ting
He
H
Ke
Dong
D
Huizhong
Zhang
Z
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015820:Cadherins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D012330:RNA, Double-Stranded / Q000627:therapeutic use*; D014162:Transfection; D015854:Up-Regulation
D015820:Cadherins; D012330:RNA, Double-Stranded