Delineating the roles of HOXB13 X285K variant in prostate cancer

Abstract

HOXB13 X285K is a frameshift mutant due to the deletion of one nucleotide, c.853delT, within the HOXB13 stop codon, resulting in an extension of HOXB13 protein by 96 amino acids on the C terminus. It was found primarily in men of West African ancestry and associated with early-onset prostate cancer (PCa) and more advanced stage. Whether and how X285K contributes to PCa progression remains largely unknown. Here, we established isogenic 22Rv1 cell lines with heterozygous wildtype/X285K HOXB13, which recapitulates the genotypes of X285K in PCa patients. In addition, using the unique C-terminal region as an antigen, we developed an antibody that specifically recognizes the HOXB13 X285K protein. Lastly, we demonstrated that X285K retained the function of HOXB13 in suppressing target genes, such as FASN and PSA. In summary, our data suggest that the isogenic cell lines and the antibody generated in this study will be useful for a comprehensive investigation of X285K function in PCa.