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Updated: May 27, 2026

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Role of JNK in mammary gland development and breast cancer
Cristina Cellurale1, Nomeda Girnius, Feng Jiang
1Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Abstract:
cJun NH(2)-terminal kinase (JNK) signaling has been implicated in the developmental morphogenesis of epithelial organs. In this study, we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast development and tumorigenesis. JNK1/2 was not required for breast epithelial cell proliferation or motility. However, JNK1/2 deficiency caused increased branching morphogenesis and defects in the clearance of lumenal epithelial cells. In the setting of breast cancer development, JNK1/2 deficiency significantly increased tumor formation. Together, these findings established that JNK signaling is required for normal mammary gland development and that it has a suppressive role in mammary tumorigenesis.
Insights
cJun NH(2)-terminal kinase (JNK) signaling is crucial for normal mammary gland development. Loss of JNK1/2 in mice increased breast tumor formation, indicating JNK signaling suppresses breast cancer development.
Area of Science:
- Cell Biology
- Developmental Biology
- Cancer Research
Background:
- cJun NH(2)-terminal kinase (JNK) signaling pathways are involved in epithelial organ development.
- The specific role of JNK1 and JNK2 in mammary gland development and tumorigenesis is not fully understood.
Purpose of the Study:
- To investigate the role of JNK1 and JNK2 in mouse mammary gland development.
- To determine the impact of JNK1/2 deficiency on mammary gland morphogenesis and epithelial cell dynamics.
- To evaluate the effect of JNK1/2 loss on breast cancer development and progression.
Main Methods:
- Compound deletion of Jnk1 and Jnk2 genes in the murine mammary gland.
- Assessment of breast epithelial cell proliferation and motility.
- Analysis of branching morphogenesis and lumenal epithelial cell clearance.
- Evaluation of mammary tumor formation in JNK1/2 deficient mice.
Main Results:
- JNK1/2 was not essential for breast epithelial cell proliferation or motility.
- JNK1/2 deficiency led to enhanced branching morphogenesis.
- Defects in lumenal epithelial cell clearance were observed in JNK1/2 deficient mammary glands.
- Loss of JNK1/2 significantly increased mammary tumor incidence.
Conclusions:
- JNK signaling is required for proper mammary gland development.
- JNK1/2 plays a suppressive role in mammary tumorigenesis.
- Targeting JNK pathways may offer therapeutic strategies for breast cancer.
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