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Updated: Oct 19, 2025
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
Published on: April 27, 2018
Targeting AP-1 transcription factors by CRISPR in the prostate
Maria Riedel1, Huiqiang Cai1, Iben C Stoltze2
1Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Abstract:
Prostate cancer is the second most diagnosed cancer in men. It is a slow progressing cancer, but when the disease reaches an advanced stage, treatment options are limited. Sequencing analyses of cancer samples have identified genes that can potentially drive disease progression. We implemented the CRISPR/Cas9 technology to simultaneously manipulate multiple genes in the murine prostate and thus to functionally test putative cancer driver genes in vivo. The activating protein-1 (AP-1) transcription factor is associated with many different cancer types, with the proto-oncogenes JUN and FOS being the two most intensely studied subunits. We analyzed expression of FOS and JUNB in human prostate cancer datasets and observed decreased expression in advanced stages. By applying CRISPR/Cas9 technology, the role of these two transcription factors in prostate cancer progression was functionally tested. Our data revealed that loss of either JunB or Fos in the context of Pten loss drives prostate cancer progression to invasive disease. Furthermore, loss of Fos increases Jun expression, and CRISPR inactivation of Jun in this context decreases cell proliferation. Overall, these in vivo studies reveal that JunB and Fos exhibit a tumor suppressor function by repressing invasive disease, whereas Jun is oncogenic and increases cell proliferation. This demonstrates that AP-1 factors are implicated in prostate cancer progression at different stages and display a dual function as tumor suppressor and as an oncogene in cancer progression.
Insights
Activating protein-1 (AP-1) factors JunB and Fos suppress prostate cancer invasion, while Jun promotes proliferation. This study reveals their dual role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer is a leading cancer in men with limited advanced-stage treatment options.
- Activating protein-1 (AP-1) transcription factors, including JUN and FOS, are implicated in various cancers.
- Understanding gene drivers is crucial for developing new prostate cancer therapies.
Purpose of the Study:
- To functionally test the role of AP-1 factors JUN and FOS in prostate cancer progression using CRISPR/Cas9 technology.
- To investigate the in vivo function of JunB and Fos in the context of Pten loss in murine prostate cancer models.
- To elucidate the dual role of AP-1 factors in different stages of prostate cancer.
Main Methods:
- Utilized CRISPR/Cas9 gene editing technology for simultaneous gene manipulation in murine prostate.
- Analyzed expression of FOS and JUNB in human prostate cancer datasets.
- Performed in vivo functional studies to assess the impact of gene alterations on prostate cancer progression.
Main Results:
- Loss of JunB or Fos, in conjunction with Pten loss, accelerates prostate cancer to invasive disease.
- Fos loss leads to increased Jun expression; Jun inactivation reduces proliferation in this context.
- JunB and Fos demonstrate tumor suppressor functions by inhibiting invasion, while Jun acts as an oncogene promoting proliferation.
Conclusions:
- AP-1 factors play a significant role in prostate cancer progression at various stages.
- JunB and Fos act as tumor suppressors, inhibiting invasive disease.
- Jun exhibits oncogenic properties, driving cell proliferation, highlighting the complex, dual function of AP-1 factors in prostate cancer.
Related Concept Videos
01:59CRISPR
01:28CRISPR/Cas9 Genome Editing
02:23Abnormal Proliferation