Delineating the roles of HOXB13 X285K variant in prostate cancer

TL;DR

This study investigates how a genetic variant in HOXB13 contributes to prostate cancer, showing it retains key regulatory functions and provides tools for further research.

Contribution

The study introduces isogenic cell lines and a specific antibody for studying the HOXB13 X285K variant in prostate cancer.

Findings

X285K retains the transcriptional regulation ability of wildtype HOXB13.

An antibody was developed to specifically recognize the X285K protein.

Isogenic cell lines with X285K were established for functional studies.

Abstract

HOXB13 X285K is a frameshift mutant caused by 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 of X285K as an antigen, we developed an antibody that specifically recognizes the HOXB13 X285K protein. Lastly, we demonstrated that X285K, similar to wildtype HOXB13, was able to rescue the effects of HOXB13 knockdown on both induced and repressed genes, such as FASN and PSA, in PCa cells. In summary, our study reports that X285K retained the transcriptional regulation ability of wildtype HOXB13 and provides isogenic PCa cell lines with wildtype and/or X285K HOXB13 expression and an X285K-specific antibody for a comprehensive investigation of X285K function in PCa.

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