Cells (Jul 2022)

Uridine Diphosphate Glucuronosyl Transferase 2B28 (UGT2B28) Promotes Tumor Progression and Is Elevated in African American Prostate Cancer Patients

  • Anindita Ravindran,
  • Kimiko L. Krieger,
  • Akash K. Kaushik,
  • Hélène Hovington,
  • Sadia Mehdi,
  • Danthasinghe Waduge Badrajee Piyarathna,
  • Vasanta Putluri,
  • Paul Basil,
  • Uttam Rasaily,
  • Franklin Gu,
  • Truong Dang,
  • Jong Min Choi,
  • Rajni Sonavane,
  • Sung Yun Jung,
  • Lisha Wang,
  • Rohit Mehra,
  • Nancy L. Weigel,
  • Nagireddy Putluri,
  • David R. Rowley,
  • Ganesh S. Palapattu,
  • Chantal Guillemette,
  • Louis Lacombe,
  • Éric Lévesque,
  • Arun Sreekumar

DOI
https://doi.org/10.3390/cells11152329
Journal volume & issue
Vol. 11, no. 15
p. 2329

Abstract

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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.

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