RESUMO
The aim of the present work was to study the immune profiling of prostate epithelial cells by the expression of ASK-1/p38 and Raf-1/ERK MAP Kinases signaling pathways mediated by TRAF-6. Immunohistochemical and Western blot analyses for TRAF-6, ASK-1, MEK-6, p38, Raf-1, MEK-1, ERK-1, ERK-2 and PSA were carried out in 5 samples of normal prostate gland, 24 samples of BPH and 19 samples of PC. Immunoreaction to TRAF-6 was found in the cytoplasm of epithelial cells of BPH and tumor cells of PC samples. For patients with the profile (TRAF-6+), optical densities revealed a weak immunoexpression of ASK-1 in PC compared to BPH patients. Whereas, immunoexpression to Raf-1 was higher in PC than in BPH. According to the expression of ASK-1 and Raf-1, two main profiles were identified: (TRAF-6+, ASK-1+, Raf-1+) and (TRAF-6+, ASK-1+, RAF-1-) in both BPH and PC. In addition, ASK-1/p38 axis expression was increased in BPH. Raf-1/ERK signaling pathway was increased in PC samples. On the other hand, representing of individual signaling protein expression enclosing each of p38 and ERK MAP Kinases according to TRAF-6+ showed a qualitative behavior of ASK61/p38 and Raf-1/ERK signaling pathways and a dynamic expression of PSA associated with immune and inflammatory process. These findings suggest that prostate epithelial cell could able an immune and inflammatory setting.
Assuntos
Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Fator 6 Associado a Receptor de TNF/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Células Epiteliais/imunologia , Células Epiteliais/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , MAP Quinase Quinase 6/genética , MAP Quinase Quinase 6/imunologia , MAP Quinase Quinase Quinase 5/genética , MAP Quinase Quinase Quinase 5/imunologia , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/imunologia , Proteína Quinase 3 Ativada por Mitógeno/imunologia , Próstata/imunologia , Próstata/patologia , Hiperplasia Prostática/imunologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/imunologia , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologiaRESUMO
Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.
Assuntos
Humanos , Amplificação de Genes , Genoma , Infecções por Herpesviridae , /genética , Neoplasias do Colo do Útero/genética , Infecções por Papillomavirus , /genética , Fatores de Risco , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase/métodos , Eletroforese , Métodos , Pacientes , PrevalênciaRESUMO
Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.
RESUMO
OBJECTIVE: The aim of this present study was to use Luminex technology to detect antibodies against the late antigen L1 as well as those directed against the early antigens E6 and E7. BACKGROUND DATA: Human papillomavirus (HPV) serology is complex because infection and disease lead to distinct type-specific antibody responses. MATERIALS AND METHODS: Viral antigens were expressed with pGEX vectors in Escherichia coli and then used in Luminex as coating antigens for antibody detection in 205 human sera samples: 71 cervical cancer cases, 64 cases of cervical inflammation, and 70 controls. RESULTS: The data showed that 90.14% of sera among the cervical cancer patients had seropositivity toward at least one of the HPV 16 or HPV 18 antigens. Moreover, the percentages of positivity toward E6 and E7 HPV 16 antigens were 44% and 61%, respectively, versus only 21% for the L1 antigen. Among cervical cancer patients, the data showed different distributions in women of different ages. In addition, the intensity of the antibody response was also different for the six antigens analyzed. CONCLUSIONS: Antibody detection depends on the type of antigen, and is well correlated with international scientific findings. The differences in antibody response between patients with inflammation and patients with cervical cancer were significant.