RESUMEN
BACKGROUND: Survivin, a novel member of the inhibitor of apoptosis family, plays an important role in cell cycle regulation. A common polymorphism at the survivin gene promoter (G/C at position 31) was shown to be correlated with survivin gene expression in cancer cell lines. AIM: To investigate whether this polymorphism could be involved in the development of human papillomavirus (HPV)-associated cervical carcinoma. METHODS: Survivin promoter polymorphism was detected in patients with cervical cancer, in patients with equivocal cytological atypia and in a control population using polymerase chain reaction (PCR-restriction fragment length polymorphism (RFLP) and PCR-single strand conformation polymorphism analysis. HPV was typed in patients with cervical cancer and cytological atypia using PCR-RFLP. RESULTS: No statistically significant differences were found in the genotype distributions of the survivin promoter variants among our study groups. CONCLUSIONS: The survivin promoter polymorphism at position 31 may not represent an increased risk for the development of cervical cancer, at least in the population studied here.
Asunto(s)
Transformación Celular Neoplásica/genética , Proteínas Asociadas a Microtúbulos/genética , Proteínas de Neoplasias/genética , Polimorfismo Genético , Neoplasias del Cuello Uterino/genética , Transformación Celular Neoplásica/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Proteínas Inhibidoras de la Apoptosis , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Neoplasias/metabolismo , Infecciones por Papillomavirus/complicaciones , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Regiones Promotoras Genéticas/genética , Survivin , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virologíaRESUMEN
The effect of the human papillomavirus type 16 (HPV 16) E6 and E7 proteins was studied on the transcriptional activity of the human transforming growth factor beta2 (TGF-beta) promoter in different cell lines. Luciferase tests were performed after co-transfection of cells with TGF-beta2 reporter constructs and HPV 16 E6 or E7 expression vectors. HPV 16 E7, but not E6 significantly repressed TGF-beta2 promoter activity in NIH/3T3 cells, which have wild-type p53 and pRb proteins. The repressive effect of HPV 16 E7 on the transcriptional activity of the TGF-beta2 promoter could be localized to the promoter region -528 to -251 relative to the transcriptional start site. Ability of E7 to bind pRb was necessary to inhibit the TGF-beta2 promoter. Over-expression of the transcription factor E2F-1 had an effect on the TGF-beta2 promoter similar to that of E7, which may indicate that HPV 16 E7 represses the TGF-beta2 promoter by releasing E2F from pRb.
Asunto(s)
Proteínas Oncogénicas Virales/fisiología , Papillomaviridae/fisiología , Proteínas Represoras/fisiología , Factor de Crecimiento Transformador beta/genética , Células 3T3 , Animales , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Viral de la Expresión Génica/fisiología , Genes Reporteros , Células HeLa , Humanos , Ratones , Proteínas E7 de Papillomavirus , Regiones Promotoras Genéticas , Unión Proteica , Transcripción Genética/fisiología , Factor de Crecimiento Transformador beta/biosíntesisRESUMEN
TT virus (TTV) genogroup 1 infection has an increased prevalence in solid organ transplant recipients. In this study, the presence of TTV in renal transplant recipients was examined by two PCR methods, one capable of detecting most TTV genotypes (UTR-PCR), the other specific to genogroup 1 (N22-PCR). The N22-PCR detected TTV in 57% (53/92) of the renal transplant patients and in 20% (13/66) of the healthy individuals, while the prevalence of TTV with the UTR-PCR was above 90% in both the control and the patient groups. The N22-PCR was used in longitudinal studies of 31 renal transplant recipients, these PCR products were sequenced and aligned. TTV status was not associated with the patients' age at transplantation, male to female ratio and the time lag between kidney transplantation and the TTV test. During the follow-up consistent TTV status was found in 26 patients, while two initially TTV positive patients converted to negative and three initially negative patients converted to positive. The TTV variants varied among the tested patients, but were the same in the consecutive samples of each patient, indicating that TTV infection was persistent in renal transplant recipients and novel infection occurred rarely in the post-transplant period.
Asunto(s)
Variación Genética , Trasplante de Riñón , Torque teno virus/genética , Torque teno virus/aislamiento & purificación , Adolescente , Adulto , Infecciones por Virus ADN/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Polimorfismo Conformacional Retorcido-Simple , PrevalenciaRESUMEN
Transcription of the E6 and E7 viral oncogenes of human papillomavirus (HPV) type 16 is regulated by the P97 major early promoter, and enhancer and silencer elements found in the long control region (LCR). In this study, we tested the transcriptional activity of natural HPV 16 variants having long deletions in the LCR. The HPV 16 LCR regions were amplified from invasive cervical cancer specimens, and cloned into the reporter vector pALuc. Transcriptional activity of the different clones was measured by luciferase test after transient transfection into HeLa cells. The deletions found in the LCR encompassed parts of the enhancer and either the YY1-specific silencer alone or together with the CDP-specific silencer. The transcriptional activity of these deletion variants were usually reduced compared with that of the corresponding full-length clones. However, a deletion variant lacking the whole enhancer and both silencer regions retained substantial enhancer activity on the P97 promoter. These results point to the existence of a novel context-dependent enhancer element in the 5' LCR of HPV 16.