Identification of prostatic-secreted proteins in mice by mass spectrometric analysis and evaluation of lobe-specific and androgen-dependent mRNA expression

Abstract

Rats and guinea pigs have frequently been used to study the development of the prostate and the mechanism of androgen action, but the mouse prostate has also become an attractive model for prostate research, because an enormous range of genetically altered mice is now available. However, the secretion of proteins in the mouse prostate has not yet been thoroughly investigated. In the present study, major secreted proteins from the ventral prostate (VP), dorsolateral prostate (DLP), and anterior prostate (AP) of mice were identified by means of 2D-gel electrophoresis followed by MALDI-TOF mass spectrometric analysis. A quantitative reverse transcriptase-PCR method was further employed to examine the androgen-dependent transcriptional regulation of the identified proteins. Proteome analysis revealed that the VP secretes spermine-binding protein, serine protease inhibitor Kazal type-3, and a 91 kDa hypothetical scavenger receptor (AK035662). DLP and AP secrete a protein similar to immunoglobulin-binding protein, immunoglobulin-binding protein-like protein, and one of the experimental autoimmune prostatitis antigen proteins (EAPA2). Peroxiredoxin-6, glucoseregulated protein 78, zinc-a2-glycoprotein, and phospholipase Ca are also secreted. Castration of animals led to a decrease in the mRNAs of these secreted proteins, although the extents of changes varied greatly among different lobes. We present here an outlined view of mouse prostate secretion, which should contribute to an understanding of the biological functions of the prostate gland, as well as the androgen dependency of prostate secretion.

Lobe-Specific Carcinogenesis in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Mouse Model

“…The expression pattern of GRP78 and clusterin were validated by immuno-blots [17]. The mRNA abundances of prostatic proteins in each lobe of mice or rats have been investigated by Fujimoto et al and Berquin et al using PCR and microarray, respectively [38][39][40]. Our results not only agreed with theirs but also extended to more lobe specific proteins.…”

Proteomic Profiling of Potential Molecular Targets of Methyl-Selenium Compounds in the Transgenic Adenocarcinoma of Mouse Prostate Model

“…In addition to the prostate differentiation and AR-regulated signaling proteins, many of the MSeA-modulated proteins are involved in protein folding (misfolding) and ER stress responses such as PDIs, PPIB, and GRP170. Some of them have been reported to be expressed or functionally related to prostate cancer (28,29,32,46). Expression of PDI was significantly reduced upon castration in male mouse DLP lobe and partially reversed upon testosterone treatment (28), and the same trends for GRP78 were observed in rats recently (32).…”

“…Some of them have been reported to be expressed or functionally related to prostate cancer (28,29,32,46). Expression of PDI was significantly reduced upon castration in male mouse DLP lobe and partially reversed upon testosterone treatment (28), and the same trends for GRP78 were observed in rats recently (32). GRP170, the largest ER resident chaperone, enhanced the therapeutic effect of tumor suppressor mda-7/interleukin 24 against TRAMP C2 allografts in a gene therapy trial (47).…”

“…MSeA partially restored the expression of proteins related to prostate functional differentiation and AR signaling, e.g., probasin, calreticulin (28,29), protein folding (misfolding), and ER stress responses, e.g., GRP78, GRP170, peptidylprolyl isomerase B, different PDI family proteins and DnaJ (Hsp40) homologue, subfamily C, member 3 (no. 58-68).…”

Lectin-binding sites in epithelial cells of the mouse prostate gland

“…These lobes differ in terms of their histological examinations, ductal patterns, and secretory functions 3,4) . Epithelial cells lining the prostatic lumen are primarily composed of luminal cells and basal cells.…”