van der Heul-Nieuwenhuijsen Leonie, Dits Natasja F, Jenster Guido
Department of Urology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, the Netherlands.
BJU Int. 2009 Jun;103(11):1574-80. doi: 10.1111/j.1464-410X.2009.08351.x. Epub 2009 Feb 11.
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.
目的 评估叉头转录因子（FOX）在正常前列腺组织及前列腺疾病中的表达情况，因为自首个FOX被鉴定以来，其家族成员已被证明参与多种细胞过程，包括胚胎发育和疾病发生。材料与方法 我们通过定量逆转录-聚合酶链反应分析了前列腺不同区域、前列腺癌、淋巴结转移灶、良性前列腺增生（BPH）、异种移植瘤及几种前列腺细胞系中的12种不同FOX基因。结果 不同FOX家族成员的表达存在显著差异；最突出的是FOXF1和FOXF2在正常前列腺移行区和BPH中高表达，而在前列腺癌中表达降低。有趣的是，尽管FOXF基因是基质特异性的，但一些雄激素非依赖性前列腺癌异种移植瘤却独特地表达这两个基因。FOXD1和FOXD2在前列腺癌及淋巴结转移灶中表达更高。FOXA1和FOXC1在雄激素依赖性前列腺癌细胞系和异种移植瘤中的表达模式相反。结论 FOX家族的不同成员在正常前列腺各区域以及良性和恶性病变中表达存在差异。FOXF1和FOXF2的表达谱提示其在上皮-间质转化中发挥作用，而FOXA1和FOXC1的表达与癌症的雄激素相关生长状态有关。
