期刊
CANCER LETTERS
卷 504, 期 -, 页码 49-57出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.01.029
关键词
Androgen receptor; Bladder cancer; Apoptosis; Splice variants; Isoforms
类别
资金
- VA MERIT awards [BX00004000, BX003458]
Bladder cancer cells express low molecular weight AR isoforms, including a novel AR-LMW variant AR-v19, which play a role in promoting cell survival and transcriptional activation in the nucleus. Targeting AR or its downstream effectors may be a potential therapeutic strategy for treating this malignancy.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据