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Updated: May 15, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
Deletion of leucine zipper tumor suppressor 2 (Lzts2) increases susceptibility to tumor development
Daniel T Johnson1, Richard Luong, Suk Hyung Lee
1Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5328, USA.
Abstract:
Using an Lzts2 knock-out mouse model, we characterized the biological role of Lzts2 in tumorigenesis. Both heterozygous and homozygous deletion of the Lzts2-targeted allele in mice shows an increased incidence in spontaneous tumor development, although Lzts2 homozygous knock-out mice show significantly higher incidences than heterozygous mice. Treatment of Lzts2-deficient mice with a carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine, increases the susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinoma development. Examination of human prostate cancer tissue specimens shows a reduction of LZTS2 protein expression in prostate cancer cells. Further analyses of mouse embryonic fibroblasts isolated from Lzts2 knock-out embryos show that loss of Lzts2 enhances cell growth. These data provide the first line of evidence demonstrating that deletion of Lzts2 increases susceptibility to spontaneous and carcinogen-induced tumor development.
Insights
Loss of the Lzts2 gene in mice increases tumor development. This study demonstrates that Lzts2 deficiency promotes both spontaneous and carcinogen-induced tumor formation, highlighting its role in cancer prevention.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The LZTS2 protein's function in tumor suppression is not fully understood.
- Genetic alterations in LZTS2 may contribute to cancer development.
Purpose of the Study:
- To investigate the biological role of Lzts2 in tumorigenesis using a mouse model.
- To determine the impact of Lzts2 deletion on spontaneous and carcinogen-induced tumor development.
Main Methods:
- Generation and characterization of Lzts2 knock-out mouse models (heterozygous and homozygous).
- Administration of N-butyl-N-(4-hydroxybutyl) nitrosamine to induce bladder carcinoma.
- Analysis of LZTS2 protein expression in human prostate cancer tissues.
- Assessment of cell growth in mouse embryonic fibroblasts derived from Lzts2 knock-out embryos.
Main Results:
- Lzts2 deletion, both heterozygous and homozygous, significantly increased spontaneous tumor incidence in mice.
- Homozygous Lzts2 knock-out mice exhibited a higher tumor incidence than heterozygous mice.
- Lzts2-deficient mice showed increased susceptibility to carcinogen-induced bladder carcinoma.
- Reduced LZTS2 protein expression was observed in human prostate cancer tissues.
- Loss of Lzts2 enhanced cell growth in mouse embryonic fibroblasts.
Conclusions:
- Lzts2 acts as a tumor suppressor, and its deletion increases susceptibility to tumor development.
- The absence of Lzts2 promotes both spontaneous and carcinogen-induced tumorigenesis.
- LZTS2 deficiency may play a role in human prostate cancer progression.
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