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  • ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms.

ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms.

Cancer research (2015-10-17)
Phillip L Palmbos, Lidong Wang, Huibin Yang, Yin Wang, Jacob Leflein, McKenzie L Ahmet, John E Wilkinson, Chandan Kumar-Sinha, Gina M Ney, Scott A Tomlins, Stephanie Daignault, Lakshmi P Kunju, Xue-Ru Wu, Yair Lotan, Monica Liebert, Mats E Ljungman, Diane M Simeone
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human ATM
Sigma-Aldrich
MISSION® esiRNA, targeting human DNMT3A
Sigma-Aldrich
MISSION® esiRNA, targeting human TRIM29
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Dnmt3a