17β-hydroxysteroid dehydrogenase type 11 (Pan1b) expression in human prostate cancer

Abstract

Androgens are reported to be actively produced in situ in human prostate cancer. These locally produced androgens are also demonstrated to play important role in the pathogenesis and development of human prostate cancer. The status of locally produced androgen inactivation and metabolism, however, remains unclear. Therefore, it is important to examine the status of this in situ androgen metabolism and inactivation in order to improve clinical response to endocrine therapy in the patients diagnosed with prostate cancer. 17β-hydroxysteroid dehydrogenase type 11 (Pan1b) was demonstrated to display greatest activity with 5α-androstan-3α, 17β-diol (3α-diol) as substrate in several human androgen metabolizing tissues, suggesting that this enzyme may play important role in androgen metabolism. However, its details including the expression level of Pan1b have not been studied in human prostate cancer. In this study, we evaluated immunolocalization of Pan1b in human prostate cancer specimens obtained from surgery (n=40), and correlated the findings with clinicopathological features of the patients in order to study its clinical significance. Pan1b immunoreactivity was detected in 19 cases (48%) and was significantly associated with cancer of seminal vesicle invasion (P<0.05). These data suggest that Pan1b expression could be connected wth advanced prostate cancer.Key words: 17ß-hydroxysteroid dehydrogenase type XI, prostate cancer, immunochemistry * Corresponding author Androgens play important role in the pathogenesis of human prostate cancer [1]. In situ production of androgens has been also suggested to play a pivotal role in the pathogenesis and/ or development of human prostate cancer [1,2]. Suppression of androgen secretion and/or a blockade of their actions represent the basis for many forms of effective hormonal treatment of the patients diagnosed with prostate cancer [3]. However, the status of further metabolism or inactivation of these locally produced androgens still remains unclear. Therefore, it becomes very important to examine the levels of expression of androgens metabolizing and inactivating enzymes in the prostate cancer tissue in order to obtain a better understanding of the possible roles of in situ androgen metabolizing.Human 17β-hydroxysteroid dehydrogenase type 11 (Pan1b) is known to display greatest activity with 5α-androstan-3α, 17β-diol (3α-diol) as substrate and to convert it to androsterone in several human androgen metabolizing tissues, suggesting its possible roles in human androgen metabolism [4,5]. 3α-diol is known to be capable of stimulating cell proliferation in androgen-sensitive prostate cancer cell line (LNCaP) [6]. Laplante et al. demonstrated that Pan1b mRNA level was higher than that of 17β-hydroxysteroid dehydrogenase type 5 (AKR1C3), one of androgen-producing enzymes in LNCaP cells [6]. However, the status of this Pan1b in human prostate cancer has not been studied at all. Therefore, in this study, we examined Pan1b immunoreactivity in human prostate cancer, and correlated the ...

Effective knowledge management in translational medicine

“…: false discovery rate estimation by the Benjamini and Hochberg procedure [25]). Searching for evidence in PubMed for association between HSD17B11 and melanoma brings up no hits but is associated with seminal vesicle invasion in prostate cancer [26]. TranSMART system also enables doing a thorough search across multiple databases for evidence of a gene's involvement in biological processes and experiments as illustrated in Figure 5.…”

Transcriptional regulation of type 11 17β-hydroxysteroid dehydrogenase expression in prostate cancer cells

“…HSD17B11 expression has been shown to be higher in PC relative to normal prostate cells (Nakamura et al 2009). To better understand the mechanisms that regulate HSD17B11 gene in PC, up to 2 Kb of the 5’-flanking region of the gene were cloned into a pGL3-Basic vector to form pB11-2016.…”

“…Since HSD17B11 converts 3α-Diol into androsterone thus reducing its intracellular levels, it is possible that this enzyme also contributes to progression to androgen independence in PC. Interestingly, HSD17B11 expression has been shown to be upregulated in human PC cells (Nakamura et al 2009). Here we show that mutation of the binding sites for C/EBPα and Sp1 decreases HSD17B11 promoter activity to less than 20% in PC cells (Fig.…”

“…HSD17B11, also known as short-chain dehydrogenase/reductase (SDR family) member 8 (DHRS8) and Pan1b, is nearly ubiquitously expressed being highly detected in lung, eyes, liver, pancreas, intestine, kidney, adrenal gland, heart, testis, ovary, placenta and sebaceous gland (Brereton et al 2001; Chai et al 2003). Importantly, a recent study demonstrates that HSD17B11 is abundantly expressed in human prostate cancer tissue but not in the normal prostate, suggesting that its expression could be connected with advanced prostate cancer (Nakamura et al 2009). …”

Cloning, characterization, and expression analysis of a putative 17 beta-hydroxysteroid dehydrogenase 11 in the abalone, Haliotis diversicolor supertexta

“…Recent investigations demonstrated that 17␤-HSD-11 can be up-regulated significantly by peroxisome proliferator-activated receptor (PPAR␣) agonists in mouse intestine, indicating that this enzyme is also involved in the lipid metabolic pathways of mouse [19][20][21]. 17␤-HSD-11 has a broad tissue distribution in humans as it was detected in the pancreas, kidney, liver, and lung as well as steroidogenic cells [17], and is also found in an androgen-dependent prostate cancer cell line [22,23].…”