Expression and Androgenic Regulation of Human Prostate‐Specific Kallikreins

BACKGROUND In an effort to identify biomarker(s) for prostatic cancer (PCa), we analyzed the changes of secretory proteins in the ventral prostate (VP) of Noble rats at early stages of carcinogenesis. METHODS Ventral prostates were removed from both control (n = 36) and experimental (n = 88) rats implanted with a known ratio of testosterone (T) and 17β‐estradiol (E2). Tissue sections were stained by hematoxylin and eosin (H&E) for pathological screening, and secretions were collected for SDS‐PAGE analysis followed by N‐terminal microsequencing, antiserum production, Western blot, and immunohistochemical study. RESULTS Pathologically, low‐grade prostatic intraepithelial neoplasia (LGPIN) and high‐grade PIN (HGPIN) were observed in ducts or alveoli after 3 and 5 months of T + E2 treatment, respectively. The results of SDS‐PAGE showed an elevated expression of 18‐kDa protein (p18) in secretions of VP with HGPIN or cancerous lesions. Analysis of p18 by N‐terminal sequencing showed a high score of homology to rat glandular kallikrein. To characterize the expression pattern of the protein in tissue samples, an antiserum was raised against the N‐terminus of the p18. The monospecificity of the antiserum against p18 was confirmed by Western blot analysis. Immunohistochemical study showed that in ducts or alveoli of normal and LGPIN samples, a mild positive staining for p18 was observed in secretions. However, the reactivity was intense not only in luminal secretions but also in some luminal secretory cells in HGPIN and cancer cells as well. CONCLUSIONS The high expression of p18 in connection with neoplastic transformation of cells strongly suggests that the potential application of this protein as a marker for early detection of PCa should be further investigated. Prostate 42:8–17, 2000. © 2000 Wiley‐Liss, Inc.

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Expression analysis of thirty one Y chromosome genes in human prostate cancer

Lau

Zhang

2000

Mol. Carcinog.

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Rapid advances in positional cloning studies have identified most of the genes on the human Y chromosome, thereby providing resources for studying the expression of its genes in prostate cancer. Using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) procedure, we had examined the expression of the Y chromosome genes in a panel of prostate samples diagnosed with benign prostatic hyperplasia (BPH), low and/or high grade carcinoma, and the prostatic cell line, LNCaP, stimulated by androgen treatment. Results from this expression analysis of 31 of the 33 genes, isolated so far from the Y chromosome, revealed three types of expression patterns: i) specific expression in other tissues (e.g., AMELY, BPY1, BPY2, CDY, and RBM); ii) ubiquitous expression among prostate and control testis samples, similar to those of house-keeping genes (e.g., ANT3, XE7,ASMTL, IL3RA, SYBL1, TRAMP, MIC2, DBY, RPS4Y, and SMCY); iii) differential expression in prostate and testis samples. The last group includes X-Y homologous (e.g., ZFY, PRKY, DFFRY, TB4Y, EIF1AY, and UTY) and Y-specific genes (e.g., SRY, TSPY, PRY, and XKRY). Androgen stimulation of the LNCaP cells resulted in up-regulation of PGPL, CSFR2A, IL3RA, TSPY, and IL9R and down regulation of SRY, ZFY, and DFFRY. The heterogeneous and differential expression patterns of the Y chromosome genes raise the possibility that some of these genes are either involved in or are affected by the oncogenic processes of the prostate. The up- and down-regulation of several Y chromosome genes by androgen suggest that they may play a role(s) in the hormonally stimulated proliferation of the responsive LNCaP cells.

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Expression and Androgenic Regulation of Human Prostate‐Specific Kallikreins

Cited by 39 publications

References 14 publications

Effects of Ca++ mobilization on expression of androgen-regulated genes: Interference with androgen receptor-mediated transactivation by AP-1 proteins

Effects of Ca++ mobilization on expression of androgen-regulated genes: Interference with androgen receptor-mediated transactivation by AP-1 proteins

Expression of a kallikrein-like protein in prostatic intraepithelial neoplasia in ventral prostate of the noble rat

Expression analysis of thirty one Y chromosome genes in human prostate cancer

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