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HCT 116 BRCA2 -/- [46] Cell Line

Invented at Cancer Research UK Cambridge Institute

Info

Catalogue Number 153531
Antigen/Gene or Protein Targets BRCA2
Parental Line HCT 116
Host Human
Tissue Colon
Disease Keywords Colorectal carcinoma, cancer
Model Knock-Out
Relevance Homozygous knockout cell line used to investigate the effects of BRCA2 mutations in a range of cancers.

Background and Research Application
BRCA2 -/- HCT116 human colorectal carcinoma cells were generated to study the role of BRCA2 in DNA repair and to identify additional functions of the BRCA2 gene. This includes the upregulation and effect of interferon-related genes (including APOBEC3F and APOBEC3G) when the BRAC2 gene is lost. This cell line shows phenotypes consistent with previous reports, including loss of Rad51 foci in the presence of double-strand breaks, chromosomal rearrangements and elevated sensitivity to the DNA-damaging agents phleomycin and Parp1 inhibitors. BRCA2 also has a role in transcriptional activation. BRAC2 inherited mutations, predispose carriers to various early onset cancers, including breast and ovarian.
Conditional No
Research Area Cancer, DNA Damage and Repair, Drug Discovery & Development
Notes Points of Interest
Transcriptional activity of the IFN-stimulated response element (ISRE) was increased in BRCA2 knockout cells, and the expression of BRCA2 greatly decreased IFN-α stimulated ISRE reporter activity. This suggests that BRCA2 directly represses the expression of IFN-related genes through the ISRE. It has been found that there are two pathways regulating IFN-related genes in BRCA2−/− cells; one is the endogenous DNA damage in BRCA2−/− cells, the other is the direct transcriptional repression by BRCA2. The colony forming capacity of BRCA2 knockout cells was significantly reduced in the presence of either IFN-β or IFN-γ. This indicates a potential for IFN as therapeutic options in cases of BRCA2 mutations.
This cell line has been used to show DNA damage occurs in BRCA2 knockout HCT116 cells even in the absence of exogenous genotoxic stress.

HCT116 BRCA2-/- cells were created through targeted disruption of human BRCA2 by homologous recombination and deletion was confirmed by Southern Blot and Western Blot using antibodies against the C-terminus of the BRCA2 protein.

Concentration
Vial has between 1-5 million cells as standard, however this may vary.
Cellosaurus ID CVCL_AS10

References

There are 4 reference entries for this reagent.

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References: 4 entries

Xu et al. 2014. J Pathol. 234(3):386-97. PMID: 25043256.

Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells.

Europe PMC ID: 25043256

Issaeva et al. 2010. Cancer Res. 70(15):6268-76. PMID: 20631063.

Issaeva et al. 2010. Cancer Res. 70(15):6268-76. PMID: 20631063.


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References: 4 entries

Xu et al. 2014. J Pathol. 234(3):386-97. PMID: 25043256.

Up-regulation of the interferon-related genes in BRCA2 knockout epithelial cells.

Issaeva et al. 2010. Cancer Res. 70(15):6268-76. PMID: 20631063.

Issaeva et al. 2010. Cancer Res. 70(15):6268-76. PMID: 20631063.


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