metallothionein and Prostatic-Hyperplasia

Cadmium (Cd) causes various genitourinary disorders and is a carcinogen for prostate cancer. Metallothionein (MT) is a protein that detoxifies heavy metals. We evaluated changes in Cd concentration and MT expression in human prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Our goal was to clarify the relationship between Cd concentration and MT expression in prostatic diseases.. The experimental group consisted of 18 patients who underwent radical prostatectomy for CaP. The control group consisted of 35 patients who underwent transurethral resection of the prostate for BPH. Tissue samples were acquired from the gross tumor site and from resected chips. We determined Cd concentration by atomic absorption, MT expression by immunoblotting, and immunohistochemical staining. The significance of between-group differences for these outcomes was analyzed using Student's t tests.. There was no statistically significant difference in Cd concentration between the CaP and BPH groups. Immunoblots from both groups revealed a single band. The relative intensity of the MT band was 0.58 +/- 0.09 in the BPH group and 0.17 +/- 0.03 in the CaP group. MT expression in patients with BPH was 3.4-fold higher than in those with CaP.. MT may bind heavy metals and protect patients from CaP. Additional studies are needed to reveal the factors that influence the expression of MT in prostate epithelial cells, and to analyze the free and compound forms of Cd at the same time.

Topics: Aged; Cadmium; Humans; Immunohistochemistry; Male; Metallothionein; Prostatic Hyperplasia; Prostatic Neoplasms

The disturbance of zinc homeostasis featured with a significant decrease of cellular zinc level was well documented to associate with the development and progression of human prostate malignancy. We have previously reported that zinc treatment induces prostate malignant cell apoptosis through mitochondrial pathway. Metallothionein (MT) is a major receptor/donor of zinc in the cells. However, the studies on the expression of MT in association with the prostate pathological and malignant status are very limited, and the zinc regulation of MT isoform expression in prostate cells remains elusive. The goals of this study were to define the expression of endogenous MTs, the isoforms of MT 1, 2, 3 at both messenger ribonucleic acid (mRNA) and protein levels; and to investigate the zinc effect on MT expression in normal prostate, benign prostatic hyperplasia (BPH) and malignant PC-3 cells, and in relevant human tissues. Cellular MT proteins were detected by immunohistochemistry, fluorescence staining and Western blot analysis; reverse transcription polymerase chain reaction (RT-PCR) was used to determine the MT isoform-specific mRNAs.. Our results demonstrated a significant suppression of endogenous levels of MT1/2 in malignant PC-3 cells (95% reduction compared to the normal prostate cells) and in human adenocarcinoma tissues (73% MT1/2 negative). A moderate reduction of MT1/2 expression was observed in BPH. Zinc treatment remarkably induced MT1/2 expression in PC-3 and BPH cells, which was accordant with the restored cellular zinc level. MT 3, as a growth inhibitory factor, was detected and up-regulated by zinc mainly in BPH cells.. This study provided evidence of the association of attenuated MT1/2 with prostate tumor progression, and the zinc induction of MT1/2 expression resulting in cellular zinc restoration. The results suggest the potential of MT1/2 as a candidate biomarker for prostate cancer and the utilization of zinc in prostate cancer prevention and treatment.

Topics: Adenocarcinoma; Blotting, Western; Cell Line, Tumor; Fluorescent Antibody Technique; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Metallothionein; Organ Specificity; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; RNA, Messenger; Zinc

Metallothionein is a low-molecular-weight cysteine-rich protein that has the ability to bind and sequestrate heavy metal ions. It is associated with metalloregulatory functions such as cell proliferation, growth and differentiation.. To investigate the expression of metallothionein in hyperplastic, dysplastic and neoplastic prostatic lesions and to correlate its expression with histological grade of prostatic carcinoma.. The study was carried out on formalin-fixed and paraffin-wax-embedded tissue blocks from 8 patients with benign prostatic hyperplasia, 6 patients with prostatic intraepithelial neoplasia (PIN) and 30 patients with prostatic carcinoma, using the streptavidin-biotin technique. The histological grade was defined and the carcinomas were divided into low-grade (Gleason Score 2-4), 12 moderate grade (Gleason Score 5-6) and 10 high-grade (Gleason Score 7-10) carcinomas.. Patchy metallothionein staining of epithelial cells was observed in normal and benign prostatic tissues. All cases of PIN and 20 of 30 patients with prostatic carcinoma showed positive staining for metallothionein. Metallothionein expression considerably increased from low-grade to high-grade tumours. The proportion of cells staining positively for metallothionein was directly correlated with histological grade of prostatic carcinoma. The epithelial cells lack uniformity in staining intensity, but the percentage of strongly positive cells increased with the histological grade of prostatic carcinoma.. The high incidence of metallothionein expression in PIN in our study suggests that it is associated with early prostate tumorigenesis. Also, metallothionein expression was directly correlated with the histological grade of prostatic carcinoma, suggesting that metallothionein may be a useful marker for predicting the prognosis of prostate cancer.

Topics: Biomarkers, Tumor; Disease Progression; Humans; Male; Metallothionein; Neoplasm Proteins; Precancerous Conditions; Prognosis; Prostatic Hyperplasia; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Protein Isoforms

This study is conducted to detect metallothionein (MT) distribution in the epithelial cells of prostate gland from patients with benign prostatic hypertrophy and adenocarcinoma.. Prostatic tissues from patients with benign prostatic hypertrophy and adenocarcinoma were processed for immunocytochemistry using indirect peroxidase antiperoxidase procedure and primary antibody against MT. The samples were collected over a period of 2-3 years and were processed at Jordan University of Science and Technology, Irbid, Jordan in the year 2002.. All prostatic tissues showed a positive reaction for MT. In benign prostatic hypertrophy, MT was mainly localized in the nuclei of epithelial cells while in the adenocarcinoma; MT was mainly localized in the cytoplasm of the epithelial cells.. Metallothionein expression may be affected by the pathological status of the prostate. In addition, these findings could be used in diagnosing and evaluating the prognosis of different pathological conditions of the prostate.

Topics: Adenocarcinoma; Cell Nucleus; Cytosol; Epithelial Cells; Humans; Immunohistochemistry; Male; Metallothionein; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Zinc

We analyzed metallothionein (MT) in rat prostates by gel filtration and radioimmunoassay. The concentration of MT in the prostate, kidney and liver of cadmium-induced rats was measured. The concentration of MT was also measured in normal prostate, benign prostatic hyperplasia, prostate cancer and the prostatic fluids from various prostatic diseases in humans. MT was detected in rat prostates by gel filtration and radioimmunoassay. The concentration of MT (micrograms/g wet tissue) was 0.3 +/- 0.1 (S.D.) in the ventral lobe, 30.4 +/- 24.0 in the lateral lobe, 5.2 +/- 0.9 in the dorsal lobe, 25.0 +/- 6.4 in the kidney and 2.0 +/- 1.5 in the liver of the rat control group. Change in MT content in CdCl2-induced organs increased quantitatively with the dose administered. The concentration of MT (micrograms/g wet tissue) in human prostate was 99.3 +/- 121.8 in the peripheral zone (PZ), 12.0 +/- 8.5 in the preprostatic region (PR), 7.3 +/- 3.1 in the central zone (CZ), 17.5 +/- 15.0 in benign hyperplastic nodules (A) and 4.2 +/- 0.5 in cancer tissue (CA). MT concentration in PZ was very high and that of CA, low (p less than 0.05). MT concentration in prostatic fluids (ng/mg protein) was 11.5 +/- 5.7 in normal patients, 3.8 +/- 2.3 in acute prostatitis, 6.5 +/- 3.7 in chronic prostatitis with pyuria, 39.6 +/- 3.9 in chronic prostatitis without pyuria and 16.9 +/- 3.0 in benign prostatic hyperplasia. We concluded that MT in the prostate is induced by heavy metals and secreted into prostatic fluid. Possibly, it is a marker of secretory function in the prostate.

Topics: Animals; Humans; Kidney; Liver; Male; Metallothionein; Prostate; Prostatic Hyperplasia; Prostatitis; Radioimmunoassay; Rats; Rats, Inbred Strains

Metallothionein (MT) in the human prostate gland was examined. Prostatic tissues were obtained from patients of urinary bladder cancer who had received radical cystoprostatectomy. MT content was 99.3 micrograms/g wet tissue (w.t.) in the peripheral zone (PZ), 12.0 micrograms/g w.t. in the preprostatic region (PR), 7.3 micrograms/g w.t. in the central zone (CZ), 6.8 micrograms/g w.t. in the anterior fibromuscular stroma, and 29.5 micrograms/g w.t. in benign nodular hyperplasia (adenoma) by radioimmunoassay. Immunohistochemical study demonstrated that MT was localized in the cytoplasm, nuclei of glandular epithelia, and secretory products. In general, a positive immunoreaction was strong in PZ and weak in CZ. It is considered that glandular epithelial cells in PZ, PR, CZ, and adenoma may react differently to heavy metals, e.g., zinc and cadmium.

Topics: Aged; Aged, 80 and over; Epithelium; Humans; Immunohistochemistry; Male; Metallothionein; Middle Aged; Prostate; Prostatic Hyperplasia; Radioimmunoassay