RESUMO
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.
Assuntos
Expressão Gênica/genética , PTEN Fosfo-Hidrolase/genética , Proteína Smad4/genética , Sistema Urogenital/enzimologia , Fatores Etários , Animais , Feminino , Masculino , RNA Mensageiro/genética , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Fatores de TempoRESUMO
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. .
Assuntos
Animais , Feminino , Masculino , Expressão Gênica/genética , PTEN Fosfo-Hidrolase/genética , /genética , Sistema Urogenital/enzimologia , Fatores Etários , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , RNA Mensageiro/genética , Fatores de TempoRESUMO
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. .(AU)
Assuntos
Animais , Ratos , Fatores Etários , Genes/genética , Sistema Urogenital/anatomia & histologia , Puberdade/metabolismo , Testículo/anatomia & histologia , Ratos/classificaçãoRESUMO
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 (r(2)=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.
Assuntos
Colágeno Tipo III/metabolismo , Colágeno Tipo I/metabolismo , Metaloproteases/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Idoso , Análise de Variância , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Metaloproteases/genética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Fatores de TempoRESUMO
UNLABELLED: This paper aimed to evaluate the leptin role on the cellular proliferation and the expression of fibroblast growth factor 2, aromatase enzyme, and apoptotic genes in the human prostate tissue. METHODS: Fifteen samples of hyperplasic prostate tissue were divided in four symmetric parts maintained in RPMI medium supplemented with 10% fetal bovine serum, 1 ng/mL of gentamicin, and added with 50 ng/mL leptin (L) or not (C). After 3 hours of incubation, gene expression was evaluated by real time RT-PCR. Cellular proliferation was evaluated by immunohistochemistry for PCNA. RESULTS: The leptin treatment led to an increase cellular proliferation (C = 21.8 ± 0.5; L = 64.8 ± 0.9; P < 0.0001) and in the expression of Bax (C = 0.4 ± 0.1; L = 0.9 ± 0.2; P < 0.05) while Bcl-2 (C = 19.9 ± 5.6; L = 5.6 ± 1.8; P < 0.05), Bcl-x (C = 0.2 ± 0.06; L = 0.07 ± 0.02; P < 0.05), and aromatase expressions (C = 1.9 ± 0.6; L = 0.4 ± 0.1; P < 0.04) were significantly reduced. CONCLUSION: Leptin has an important role in maintaining the physiological growth of the prostate since it stimulates both cellular proliferation and apoptosis, with the decrement in the aromatase gene expression.
Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Leptina/farmacologia , Próstata/citologia , Próstata/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Próstata/metabolismoRESUMO
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.
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Metaloproteases/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Análise de Variância , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Expressão Gênica , Estimativa de Kaplan-Meier , Metaloproteases/genética , Gradação de Tumores , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Fatores de TempoRESUMO
The aim of this study was to evaluate the effect of leptin administration on the ventral prostate lobe of adult rat. Twenty adult male rats were divided into 2 groups: L-animals were daily injected with 50 µL of leptin (8 µg/100 g BW, subcutaneous) for four days and C-animals received the same volume of saline solution. Lipid profile and testosterone serum levels were evaluated. The prostate ventral lobe was processed for histomorphometric analysis. Gene expression of aromatase, androgen, leptin and estrogen receptors isoforms was evaluated by real-time PCR. Cell proliferation was evaluated by PCNA immunohistochemistry. Data were expressed as mean±standard error and analyzed by student's t-test. Serum levels of cholesterol (C=39.7±4.2;L=55.2±4.2, mg/dL; P<0.02) increased and testosterone (C=1.6±0.43;L=0.6±0.15, ng/dL; P<0.03) decreased in L group. The histomorphometric analysis showed a reduction in cell density (C=8868±242; L=8211±210, mm(2); P<0.04), in total (C=0.24±0.026; L=0.10±0.009, mm(2); P<0.001) and in the internal acini areas (C=0.16±0.009; L=0.08±0.006, mm(2); P<0.0002). On the other hand, there was an increase in the epithelial height (C=17.3±0.3; L=22.8±0.2, µm; P<0.0001) and in the number of acini (C=7.0±0.2; L=8.7±0.1, mm(2); P<0.0002). The histomorphometric analyses together with PCNA immunohistochemistry results suggest that leptin increases cell proliferation. In relation to the gene expression, leptin treatment increased the expression of all genes, but ER-α, in more than 200 times compared to the expression in C group. In conclusion, in this paper we showed that leptin has a direct effect on the prostate gland of adult rats leading to an increase in proliferation and in the gene expression of aromatase, androgen, leptin and estrogen receptors isoforms that are important for the physiology of the prostate gland.
Assuntos
Leptina/administração & dosagem , Leptina/farmacologia , Próstata/anatomia & histologia , Próstata/efeitos dos fármacos , Lobo Temporal/patologia , Androgênios/genética , Animais , Aromatase/genética , Aromatase/metabolismo , Proliferação de Células/efeitos dos fármacos , Perfilação da Expressão Gênica , Imuno-Histoquímica , Injeções Subcutâneas , Lipídeos/sangue , Masculino , Próstata/citologia , Próstata/metabolismo , Isoformas de Proteínas/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Estrogênio/genética , Receptores para Leptina/genética , Lobo Temporal/metabolismo , Testosterona/sangueRESUMO
The involvement of leptin in prostate diseases is related to an increase in the gene expression of both a and b isoform leptin receptors, leptin itself, androgen receptor, and aromatase, as well as by a reduction in both estrogen isoform receptors.