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Updated: Mar 31, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms
Phillip L Palmbos1, Lidong Wang2, Huibin Yang2
1Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan. Translational Oncology Program, University of Michigan Medical Center, Ann Arbor, Michigan.
Abstract:
Bladder cancer is a common and deadly malignancy but its treatment has advanced little due to poor understanding of the factors and pathways that promote disease. ATDC/TRIM29 is a highly expressed gene in several lethal tumor types, including bladder tumors, but its role as a pathogenic driver has not been established. Here we show that overexpression of ATDC in vivo is sufficient to drive both noninvasive and invasive bladder carcinoma development in transgenic mice. ATDC-driven bladder tumors were indistinguishable from human bladder cancers, which displayed similar gene expression signatures. Clinically, ATDC was highly expressed in bladder tumors in a manner associated with invasive growth behaviors. Mechanistically, ATDC exerted its oncogenic effects by suppressing miR-29 and subsequent upregulation of DNMT3A, leading to DNA methylation and silencing of the tumor suppressor PTEN. Taken together, our findings established a role for ATDC as a robust pathogenic driver of bladder cancer development, identified downstream effector pathways, and implicated ATDC as a candidate biomarker and therapeutic target.
Insights
The study reveals that ATDC (also known as TRIM29) drives bladder cancer development and progression. This gene acts as a key driver by silencing tumor suppressors, suggesting it
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Bladder cancer treatment remains challenging due to limited understanding of its drivers.
- The gene ATDC/TRIM29 is highly expressed in lethal tumors, including bladder cancer, but its pathogenic role is unclear.
Purpose of the Study:
- To investigate the role of ATDC/TRIM29 as a driver of bladder cancer.
- To elucidate the molecular mechanisms by which ATDC contributes to bladder cancer development and invasiveness.
Main Methods:
- Overexpression of ATDC in transgenic mice to model bladder carcinoma.
- Comparison of gene expression signatures between mouse and human bladder cancers.
- Analysis of downstream effector pathways including miR-29, DNMT3A, and PTEN.
Main Results:
- ATDC overexpression in mice was sufficient to induce both noninvasive and invasive bladder carcinomas.
- ATDC-driven tumors mirrored human bladder cancer gene expression profiles and invasive behaviors.
- ATDC was found to suppress miR-29, leading to DNMT3A upregulation, DNA methylation, and PTEN silencing.
Conclusions:
- ATDC/TRIM29 functions as a potent oncogenic driver in bladder cancer.
- The ATDC pathway involves suppression of miR-29 and silencing of the PTEN tumor suppressor.
- ATDC is a potential biomarker and therapeutic target for bladder cancer.
