Prostatic acid phosphatase (PAP) is currently evaluated as a target for vaccine immunotherapy of prostate cancer. This is based on the previous knowledge about secretory PAP and its high prostatic expression. We describe a novel PAP spliced variant mRNA encoding a type I transmembrane (TM) protein with the extracellular NH 2

Estrogens have an important role in the development and progression of breast cancer. 17␤-Hydroxysteroid dehydrogenase type 1 (17HSD1), type 2 (17HSD2), and type 5 (17HSD5) are associated with sex steroid metabolism in normal and cancerous breast tissue. The mRNA expressions of the 17HSD1, 17HSD2, and 17HSD5 enzymes were analyzed in 794 breast carcinoma specimens by using tissue microarrays and normal histologic sections. The results were correlated with the estrogen receptor ␣ (ER-␣) and ␤ (ER-␤), progesterone receptor, Ki67, and c-erbB-2 expressions analyzed by immunohistochemical techniques and with the Tumor-Node-Metastasis classification, tumor grade, disease-free interval, and survival of the patients. Signals for 17HSD1 mRNA were detected in 16%, 17HSD2 in 25%, and 17HSD5 in 65% of the breast cancer specimens. No association between the 17HSD1, 17HSD2, and 17HSD5 expressions was detected. A significant association was observed between ER-␣ and ER-␤ (P ‫؍‬ 0.02; odds ratio, 1.96) expressions. There was also a significant inverse association between ER-␣ and 17HSD1 (P ‫؍‬ 0.04; odds ratio, 0.53), as well as ER-␣ and 17HSD5 (P ‫؍‬ 0.001; odds ratio, 0.35). Patients with tumors expressing 17HSD1 mRNA or protein had significantly shorter overall and disease-free survival than the other patients (P ‫؍‬ 0.0010 and 0.0134, log rank). The expression of 17HSD5 was significantly higher in breast tumor specimens than in normal tissue (P ‫؍‬ 0.033; odds ratio, 5.56). The group with 17HSD5 overexpression had a worse prognosis than the other patients (P ‫؍‬ 0.0146). ER-␣ also associated with survival (P ‫؍‬ 0.045). Cox multivariate analyses showed that 17HSD1 mRNA, tumor size, and ER-␣ had independent prognostic significance.

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The progression of prostate cancer during androgen deprivation therapy is a serious clinical problem. Little is known, however, about the mechanisms behind the transition of the disease to an androgen-independent stage. In the present report, we provide evidence of substantial changes in both estrogen and androgen metabolism during the transition of cultured prostate cancer LNCaP (lymph node carcinoma of the prostate) cells. The results of enzyme activity measurements performed using HPLC suggest that, related to the transition, there exists a remarkable decrease in the oxidative 17 beta-hydroxysteroid dehydrogenase (17HSD) activity, whereas the reductive 17HSD activity seems to increase. Relative quantitative RT-PCR revealed that the decrease in oxidative activity largely coincided with the remarkable decrease in the expression of the HSD17B2 gene. Furthermore, the present data suggest that the observed increasing activity of 17HSD type 7 could lead to the increased intracellular production of 17 beta-estradiol during disease progression. This was supported by the cDNA microarray screening results, which showed a considerable overexpression of several estrogen up-regulated genes in the LNCaP cell line variant that represents progressive prostate cancer. Because 17HSDs critically contribute to the control of bioavailability of active sex steroid hormones locally in the prostate, the observed variation in intraprostatic 17HSD activity might be predicted to be crucially involved in the regulation of growth and function of the organ.