Uridine Diphosphate Glucuronosyl Transferase 2B28 (UGT2B28) Promotes Tumor Progression and Is Elevated in African American Prostate Cancer Patients
- PMID: 35954173
- PMCID: PMC9367340
- DOI: 10.3390/cells11152329
Uridine Diphosphate Glucuronosyl Transferase 2B28 (UGT2B28) Promotes Tumor Progression and Is Elevated in African American Prostate Cancer Patients
Abstract
Prostate cancer (PCa) is the second most diagnosed cancer in the United States and is associated with metabolic reprogramming and significant disparities in clinical outcomes among African American (AA) men. While the cause is likely multi-factorial, the precise reasons for this are unknown. Here, we identified a higher expression of the metabolic enzyme UGT2B28 in localized PCa and metastatic disease compared to benign adjacent tissue, in AA PCa compared to benign adjacent tissue, and in AA PCa compared to European American (EA) PCa. UGT2B28 was found to be regulated by both full-length androgen receptor (AR) and its splice variant, AR-v7. Genetic knockdown of UGT2B28 across multiple PCa cell lines (LNCaP, LAPC-4, and VCaP), both in androgen-replete and androgen-depleted states resulted in impaired 3D organoid formation and a significant delay in tumor take and growth rate of xenograft tumors, all of which were rescued by re-expression of UGT2B28. Taken together, our findings demonstrate a key role for the UGT2B28 gene in promoting prostate tumor growth.
Keywords: African American prostate cancer; UGT2B28; androgen signaling; glucuronidation; metabolic regulation; prostate cancer; tumorigenesis.
Conflict of interest statement
Akash Kaushik, one of the co-authors has recently moved to a company earlier this month and has declared the following conflict of interest. This conflict of interest was not there when he generated the data for this manuscript. Akash K Kaushik is currently affiliated with Internal Medicine Research Unit at Pfizer and may have stock ownership.
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