Abnormal level of retinoic acid in prostate cancer tissues

Vitamin A (retinol) and its derivatives, the retinoids, have been implicated as chemopreventive and differentiating agents in a variety of cancers, including that of the prostate. Very little is known about the physiological role of retinoids in the prostate. Here we show that normal prostate, benign prostate hyperplasia (BPH), and prostate carcinoma tissues contain endogenous retinol and its biologically active metabolite retinoic acid. In our studies, the concentration of retinol was 2-fold elevated in BPH compared with the other two tissues. In contrast, prostate carcinoma tissue contained five to eight times less retinoic acid than normal prostate or BPH. Moreover, we found that prostate tissue expresses dehydrogenases capable of converting retinol to retinoic acid through retinaldehyde as an intermediate. Formation of retinal from retinol takes place in microsomes, and the conversion of retinal to retinoic acid occurs in the cytosol. Furthermore, we found that the nuclear retinoic acid receptors alpha, beta, and gamma are expressed in normal and tumor samples. These studies establish a role for retinoids in the physiology of the prostate and possibly also in the pathophysiology of prostate cancer.