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Related Experiment Video

Updated: Mar 20, 2026

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

RANKL/RANK control Brca1 mutation- .

Verena Sigl¹, Kwadwo Owusu-Boaitey², Purna A Joshi³

¹IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna 1030, Austria.

|June 1, 2016

Summary

This summary is machine-generated.

Targeting the RANKL/RANK pathway can prevent breast cancer in BRCA1 mutation carriers. Inhibiting this pathway reduces mammary cancer onset, progression, and pre-neoplastic lesions in mouse models.

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Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

Area of Science:

Oncology
Genetics
Cell Biology

Background:

Breast cancer is a leading female cancer, with inherited BRCA1/BRCA2 mutations significantly increasing risk.
Understanding the molecular mechanisms driving hereditary breast cancer is crucial for developing preventative strategies.

Purpose of the Study:

To investigate the role of the RANKL/RANK signaling pathway in BRCA1-associated mammary tumorigenesis.
To evaluate the therapeutic potential of targeting RANKL/RANK for breast cancer prevention in BRCA1 mutation carriers.

Main Methods:

Utilized genetically engineered mouse models with Brca1;p53 mutations.
Administered pharmacological inhibition of RANKL in mice.
Assessed mammary stem cell and progenitor cell proliferation in vitro.
Analyzed genome variations within the RANK locus in human BRCA1 mutation carriers.

Main Results:

Genetic inactivation of RANK in mammary epithelium delayed mammary cancer onset and progression in Brca1;p53 mutant mice.
Long-term RANKL inhibition prevented pre-neoplastic lesions in Brca1 mutation-driven mammary cancer.
RANK/RANKL blockade impaired mammary stem cell and progenitor proliferation in murine models and human BRCA1 carriers.
Genetic variations in the RANK locus correlated with breast cancer risk in women with BRCA1 mutations.

Conclusions:

The RANKL/RANK pathway is a critical regulator of progenitor cell expansion and tumorigenesis in inherited breast cancer.
Targeting RANKL/RANK presents a promising strategy for preventing breast cancer in individuals with BRCA1 mutations.