Age-dependent expression of Pten and Smad4 genes in the urogenital system of Wistar rats

PURPOSE: To analyze Pten and Smad4 gene expression in the urogenital system of Wistar rats in differents ages. METHODS: Pten and Smad4 mRNA expression was assessed in the bladder, ventral prostate, testis, ovaries, and uterus by real-time PCR. Statistical analysis using the ANOVA (p<0.05). RESULTS: Pten levels showed a progressive age-dependent increase in the bladder (male and female) and prostate and were elevated in the ovaries of the middle-aged. In the uterus, no statistically significant differences were observed; in the testis, increased and decreased levels were seen in young adult and middle-aged rats, respectively. Smad4 expression was downregulated in the ovaries of the pubertal group but increased in the middle age group. In the uterus, Smad4 expression in the oldest group was higher than the others groups. In the testis, Smad4 expression steadily declined with age; in the prostate, it was higher in middle-aged rats than in younger rats. A similar trend was observed in the bladder of male and female middle-aged rats, compared with the pubertal group. CONCLUSION: The changes in phosphatase tensin homologue and Smad4 mRNA expression in Wistar rats appear to be associated with hormonal modifications in puberty and may be related to early follicular and testicular development. .

Collagen I and III and metalloproteinase gene and protein expression in prostate cancer in relation to Gleason score

PURPOSE: To evaluate if the expression of metalloproteinase, collagen I and III are related to Gleason score, preoperative PSA and pathological stage in prostate cancer. MATERIALS AND METHODS: Our study group included radical prostatectomy specimens of 33 patients with prostatic adenocarcinoma who underwent surgery from 2001 to 2009. Patients were divided into 3 groups: Gleason score=6 (13 patients), Gleason score=7 (10 patients), Gleason score>8 (10 patients). The control group included prostates of patients submitted to cystoprostatectomy and benign prostatic tissues adjacent to the cancer area. Specific areas of tissues were selected under microscope and further processed for collagen I and III analysis by real time PCR. In addition, 10 deparaffined sections of each group were used to evaluate collagen I, III and metalloproteinase immune expression. The results were correlated with Gleason score, preoperative PSA and pathological stage. RESULTS: We found significant difference in both collagen I and III gene expression between benign and tumoral areas in the prostate samples from Gleason score=6 (collagen I=0.4±0.2 vs 5±2.4, p<0.05; collagen III=0.2±0.06 vs 0.7±0.1, p<0.05) and Gleason score>8 (collagen I=8±3.4 vs 1.4±0.8, p<0.07; collagen III=1.8±0.5 vs 0.6±0.1, p<0.05). There was no correlation of collagen expression with Gleason score, preoperative PSA or pathological stage. There was a positive correlation between metalloproteinase expression and Gleason score (r²=0.47). CONCLUSIONS: The positive correlation between metalloproteinase expression and Gleason score suggests that metalloproteinase could be a promising factor to improve Gleason score evaluation. Its expression and regulation do not seem to be related with collagen degradation.