Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells

International Journal of Molecular Sciences

Irida Kastrati¹  Li Liu²  Heidi Wang²  Alan M. Diamond³  Mostafa Elhodaky³  Shrinidhi Kadkol³  Lenny K. Hong³  Ryan Deaton³  Maria Sverdlov³  Karen S. Sfanos⁴ 

[1] Department of Cancer Biology, Loyola University of Chicago, Cardinal Bernardin Cancer Center, Maywood, IL 60153, USA;Department of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL 60612, USA;Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA;Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;

关键词: prostate;    cancer;    selenium;    selenoprotein;    tumor suppressor;   

DOI  :  10.3390/ijms222112040

来源: DOAJ

【 摘 要 】

SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3′-untranslated (3′-UTR) region of the SELENOF mRNA. Polymorphisms in the 3′-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions. Using a prostate cancer tissue microarray, it was previously established that the reduction of SELENOF in the cancers from African American men was significantly greater than in cancers from Caucasian men. When SELENOF levels in human prostate immortalized epithelial cells were reduced with an shRNA construct, those cells acquired the ability to grow in soft agar, increased the ability to migrate in a scratch assay and acquired features of energy metabolism associated with prostate cancer. These results support a role of SELENOF loss in prostate cancer progression and further indicate that SELENOF loss and genotype may contribute to the disparity in prostate cancer mortality experienced by African American men.

【 授权许可】

Unknown