Yulu Zhang1, Lin Ye, Yuxia Tan, Pinghui Sun, Ke Ji, Wen G Jiang. 1. Metastasis and Angiogenesis Research Group, CUPUCI, Cardiff University School of Medicine, Henry Welcome Building, Heath Park, Cardiff CF14 4XN, U.K. JiangW@cardiff.ac.uk.
Abstract
UNLABELLED: Breast cancer metastasis suppressor-1 (BRMS1) is a candidate metastasis-suppressing gene and has been shown to potentially inhibit tumor progression without blocking the growth of orthotopic tumors, in different tumor types including non-small cell lung cancer, ovarian, melanoma and breast cancers. MATERIALS AND METHODS: BRMS-1 gene transcript was quantified in breast cancer sample tissues and analyzed against histological and clinical patient outcome. Human breast cancer cell lines, MDA MB-231 and MCF-7 were used to genetically-modify the expression of BRMS-1 and test for biological responses following BRMS-1 modifications. Key candidate signal pathways, influenced by BRMS-1 were also explored. RESULTS: BRMS1 was present in MDA MB-231 and MCF-7 cell lines. Using anti-BRMS1 transgenes, we knocked-down the transcripts of BRMS1 in both cells at the mRNA and protein levels. Knockdown of BRMS1 gave both cells a faster cell growth rate, rapid pace of cellular migration and invasion, compared to respective wild-type and control cells (p<0.05). Blocking phospholipase-Cγ (PLCγ) had a significant influence on the BRMS-1-induced cell migration. Finally, significantly low levels of BRMS1 were observed in patients with high-grade tumors (p=0.12), in patients with distant metastasis (p=0.05) and those who died of breast cancer (p=0.0037). In addition, patients with low levels of BRMS1 had a significantly shorter overall survival (p=0.035). CONCLUSION: BRMS-1 is aberrantly expressed in human breast cancer and is inversely-correlated with disease progression and patient survival. This is likely to be occurring via its influence on invasion and migration of breast cancer cells.
UNLABELLED: Breast cancer metastasis suppressor-1 (BRMS1) is a candidate metastasis-suppressing gene and has been shown to potentially inhibit tumor progression without blocking the growth of orthotopic tumors, in different tumor types including non-small cell lung cancer, ovarian, melanoma and breast cancers. MATERIALS AND METHODS:BRMS-1 gene transcript was quantified in breast cancer sample tissues and analyzed against histological and clinical patient outcome. Humanbreast cancer cell lines, MDA MB-231 and MCF-7 were used to genetically-modify the expression of BRMS-1 and test for biological responses following BRMS-1 modifications. Key candidate signal pathways, influenced by BRMS-1 were also explored. RESULTS:BRMS1 was present in MDA MB-231 and MCF-7 cell lines. Using anti-BRMS1 transgenes, we knocked-down the transcripts of BRMS1 in both cells at the mRNA and protein levels. Knockdown of BRMS1 gave both cells a faster cell growth rate, rapid pace of cellular migration and invasion, compared to respective wild-type and control cells (p<0.05). Blocking phospholipase-Cγ (PLCγ) had a significant influence on the BRMS-1-induced cell migration. Finally, significantly low levels of BRMS1 were observed in patients with high-grade tumors (p=0.12), in patients with distant metastasis (p=0.05) and those who died of breast cancer (p=0.0037). In addition, patients with low levels of BRMS1 had a significantly shorter overall survival (p=0.035). CONCLUSION:BRMS-1 is aberrantly expressed in humanbreast cancer and is inversely-correlated with disease progression and patient survival. This is likely to be occurring via its influence on invasion and migration of breast cancer cells.
Entities:
Keywords:
BRMS-1; PLC-γ; breast cancer; cell migration; metastasis; survival
Authors: Siti Nur Ain Roesley; Randy Suryadinata; Emma Morrish; Anthonius Ricardo Tan; Samah M A Issa; Jonathan S Oakhill; Ora Bernard; Danny R Welch; Boris Šarčević Journal: Cell Cycle Date: 2016 Impact factor: 4.534