In situ androgen producing enzymes in human prostate cancer

Abstract

Androgens have been proposed to be actively produced in situ in human prostate cancer. These locally produced androgens have also been considered to play important roles in the pathogenesis and development of prostate cancer. Therefore, it is important to examine the status of this in situ androgen metabolism and/or synthesis in detail in order to improve the clinical response to hormonal therapy in patients diagnosed with prostate cancer. Several studies have previously demonstrated the expression of androgen-producing enzymes such as 5a-reductase types 1 and 2, and 17b-hydroxysteroid dehydrogenase type 5 (17b-HSD5), in human prostate carcinoma cells. However, their biological significance has remained largely unknown. In this study, we evaluated the immunoreactivities of these steroidogenic enzymes in human prostate cancer obtained from surgery (n=70), and correlated the findings with clinicopathological features of the patients. 17b-HSD5 immunoreactivity was detected in 54 cases (77%), 5a-reductase type 1 in 51 cases (73%) and 5a-reductase type 2 in 39 cases (56%). 5a-reductase type 2 immunoreactivity was significantly correlated with that of androgen receptor (AR), and 17b-HSD5 positive cases were significantly associated with clinical stage (TNM stage pT3 vs pT2). These data all suggest that androgenproducing enzymes, such as 5a-reductase type 1 and type 2, and 17b-HSD5 are expressed in a majority of prostate cancers, and are involved in the local production and actions of androgens in prostate cancers.

Simvastatin in combination with meclofenamic acid inhibits the proliferation and migration of human prostate cancer PC‑3 cells via an AKR1C3 mechanism

“…The expression of AKR1C3 is increased in several human cancers, including kidney (15) and breast (16). Concerning prostate cancer, localized, metastatic and recurrent prostate cancer has high levels of AKR1C3 (17)(18)(19). In addition, elevated AKR1C3 expression promotes the aggressiveness of PC-3 cells, which lack AR (7).…”

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

“…Immunohistochemistry Immunohistochemical analysis was performed employing the streptavidin-biotin amplification method using a Histofine Kit (Nichirei, Tokyo, Japan) and has been previously described in detail [2]. The dilutions of primary antibodies used in our study were as follows: Pan1b, 1: 200; AR, 1: 100; ERβ, 1: 1,500; and Ki-67, 1: 50.…”

“…Scoring of immunoreactivity was performed based on previous reports [2,7,8]. For statistical analyses of Pan1b immunoreactivity, the carcinoma cases were tentatively classified into the following two groups: +, positive, more than 10% positive cells; and -, no immunoreactivity, less than 10% positive cells [2].…”

“…In each case, more than 500 carcinoma cells were counted independently by two of the authors above, and the percentage of immunoreactivity, i.e. labeling index (LI), was determined [2,7,8]. We evaluated all the slides containing carcinoma cells in each individual case.…”

“…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].…”