BRMS1 inhibits expression of NF-kappaB subunit p65, uPA and OPN in ovarian cancer cells

Breast cancer metastasis suppressor 1 (BRMS1) is a potent metastasis suppressor of various types of malignancies, including melanoma and ovarian cancer. Unfortunately, the clinical data regarding its role as a true metastatic suppressor and its efficacy as a prognostic marker and therapeutic target...

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Bibliographic Details
Published in:European journal of gynaecological oncology 2014, Vol.35 (3), p.236-242
Main Authors: Sheng, X J, Zhou, D M, Liu, Q, Lou, S Y, Song, Q Y, Zhou, Y Q
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Cell Movement
Female
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Proteins - genetics
Neoplasm Proteins - physiology
Osteopontin - antagonists & inhibitors
Osteopontin - genetics
Ovarian Neoplasms - pathology
Repressor Proteins
RNA, Small Interfering - genetics
Transcription Factor RelA - antagonists & inhibitors
Transcription Factor RelA - genetics
Urokinase-Type Plasminogen Activator - antagonists & inhibitors
Urokinase-Type Plasminogen Activator - genetics
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Summary:Breast cancer metastasis suppressor 1 (BRMS1) is a potent metastasis suppressor of various types of malignancies, including melanoma and ovarian cancer. Unfortunately, the clinical data regarding its role as a true metastatic suppressor and its efficacy as a prognostic marker and therapeutic target remain controversial. This study was designed to investigate the effect of BRMS1 on the invasion and metastasis of human ovarian cancer cells and its potential underlying mechanisms. BRMS1 small interfering RNAs (siRNAs) or control siRNAs were transfected into the OVCAR3 human ovarian cancer cell line. Invasion and migration activities were assessed using the Transwell invasion and migration assay. Protein levels of nuclear factor-kappaB (NF-kappaB) subunit p65, osteopontin (OPN) and urokinase-type plasminogen activator (uPA) were evaluated by Western blot, immunofluorescence and immunocytochemistry methods. Successful knockdown of BRMS1 was verified by quantitative real-time RT-PCR and Western blot. The invasion and migration capacities of OVCAR3 cells were significantly enhanced in the BRMS1-silenced group, compared to controls (p < 0.05). Silencing of BRMS 1 significantly induced the expression of NF-kappaB subunit, p65, uPA, and OPN proteins. BRMS1 inhibits expression of p65, uPA and OPN protein. In turn, this leads to inhibition of ovarian cancer cell invasion and metastasis. This study unveils a potential novel mechanism by which BRMS1 inhibits metastasis of ovarian cancer cells.
ISSN:0392-2936