Gene expression of forkhead transcription factors in the normal and diseased human prostate.

OBJECTIVE To assess the expression of forkhead transcription factors (FOX) in normal prostate and prostate diseases, as since the first FOX was identified, its family members have been implicated in a variety of cellular processes, including embryonic development and disease. MATERIAL AND METHODS We analysed a set of 12 different FOX genes by quantitative reverse transcription-polymerase chain reaction in prostate zones, prostate cancer, lymph node metastases, benign prostatic hyperplasia (BPH), xenografts and several prostate cell lines. RESULTS There were striking differences among the expression of various FOX family members; most prominent were the high expression of FOXF1 and FOXF2 in the normal prostate transition zone and BPH, and their decreased expression in prostate cancer. Interestingly, although the FOXF genes are stroma-specific, some of the androgen-independent prostate cancer xenografts uniquely express these two genes. FOXD1 and FOXD2 were more highly expressed in prostate cancer and lymph node metastases. FOXA1 and FOXC1 have an opposite expression pattern for androgen-dependent growth of prostate cancer cell lines and xenografts. CONCLUSIONS Various members of the FOX family are differentially expressed in the zones of the normal prostate and in benign and malignant outgrowths. The expression profiles of FOXF1 and FOXF2 suggest a role in epithelial to mesenchymal transition, while FOXA1 and FOXC1 expression is linked to androgen-associated growth status of cancer.