ArticleCancer biology & therapy2009
Reduced cell death, invasive and angiogenic features conferred by BRCA1-deficiency in mammary epithelial cells transformed with H-Ras.
Article in Cancer biology & therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
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- Convergence of therapy-induced senescence (TIS) and EMT in multistep carcinogenesis: current opinions and emerging perspectives.Cell death discovery · 2020Review
- The protective role of DMBT1 in cervical squamous cell carcinoma.The Kaohsiung journal of medical sciences · 2019Article
- BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity.Nature communications · 2016Article
- Dbl oncogene expression in MCF-10 A epithelial cells disrupts mammary acinar architecture, induces EMT and angiogenic factor secretion.Cell cycle (Georgetown, Tex.) · 2015Article
- Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis.Journal of cellular physiology · 2014Review
- Predicting therapy response in live tumor cells isolated with the flexible micro spring array device.Cell cycle (Georgetown, Tex.) · 2013Article
- Prolonged response of relapsed high grade serous ovarian carcinoma to the oral angiokinase inhibitor nintedanib in a patient with a germline BRCA1 mutation.Gynecologic oncology case reports · 2012Article
- Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis.Cancer biology & therapy · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
To investigate the role of tumor suppressors BRCA1 and p53 proteins in human breast tumorigenesis, we transformed immortalized human mammary epithelial cells, MCF10A, with or without BRCA1/p53 gene-specific knockdowns. Stable knockdown of BRCA1 alone in MCF10A cells led to centrosome amplification, impaired p53 protein stability, increased sensitivity towards DNA-damaging agents, defective chromosomal condensation at mitosis and elevated protein levels of cyclin D1 and c-myc. While over-expression of mutant H-Ras transformed MCF10A cells, depletion of BRCA1 dramatically enhanced the in vivo tumorigenesis that was associated with higher levels of VEGF, enhanced vascularization and less apoptosis in the BRCA1-deficient Ras-transformed tumors. The Ras-transformed BRCA1-deficient tumors exhibited features of the epithelial-to-mesenchymal transition, appeared to secrete matrix metalloproteases as visualized by in vivo bio-imaging of tumors using fluorescent probe MMP680, and were locally metastatic to lymph nodes. Our results suggest that loss of BRCA1 function may contribute to the aggressiveness of Ras-MAPK driven human breast cancer with associated increase in levels of cyclin D1 and c-myc, enhanced MAPK activity, angiogenic potential & invasiveness. This mammary xenograft tumor model may be useful as a tool to understand human breast tumor angiogenesis and metastasis, as well as to test candidate therapeutics.
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Registered trials
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