Depletion of androgen receptor low molecular weight isoform reduces bladder tumor cell viability and induces apoptosis
Autor: | Alexander J. Platero, Alan P. Lombard, Maria Mudryj, Paramita M. Ghosh, Ai Hong Ma, Stephen J. Libertini, Kristine S. Nishida, Chong-Xian Pan, Kimberley Katleba, Han Bit Baek, Maria Malvina Tsamouri |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Gene isoform Male Urologic Diseases Cancer Research Cell Survival Cell Oncology and Carcinogenesis Apoptosis Article Androgen 03 medical and health sciences 0302 clinical medicine Transcription (biology) Splice variants Receptors medicine Genetics Humans Viability assay Oncology & Carcinogenesis Cancer Chemistry Alternative splicing Bladder cancer Cell biology Androgen receptor Molecular Weight 030104 developmental biology medicine.anatomical_structure Oncology Urinary Bladder Neoplasms Cytoplasm Receptors Androgen 5.1 Pharmaceuticals 030220 oncology & carcinogenesis Female Development of treatments and therapeutic interventions Isoforms |
Zdroj: | Cancer Lett |
Popis: | Bladder cancer (BlCa) exhibits a gender disparity where men are three times more likely to develop the malignancy than women suggesting a role for the androgen receptor (AR). Here we report that BlCa cells express low molecular weight (LMW) AR isoforms that are missing the ligand binding domain (LBD). Isoform expression was detected in most BlCa cells, while a few express the full-length AR. Immunofluorescence studies detect AR in the nucleus and cytoplasm, and localization is cell dependent. Cells with nuclear AR expression exhibit reduced viability and increased apoptosis on total AR depletion. A novel AR-LMW variant, AR-v19, that is missing the LBD and contains 15 additional amino acids encoded by intron 3 sequences was detected in most BlCa malignancies. AR-v19 localizes to the nucleus and can transactivate AR-dependent transcription in a dose dependent manner. AR-v19 depletion impairs cell viability and promotes apoptosis in cells that express this variant. Thus, AR splice variant expression is common in BlCa and instrumental in ensuring cell survival. This suggests that targeting AR or AR downstream effectors may be a therapeutic strategy for the treatment of this malignancy. |
Databáze: | OpenAIRE |
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