Ha-ras oncogene-induced transcription of human papillomavirus type 18 E6 and E7 oncogenes.

Human papillomavirus (HPV) DNA sequences are found in most carcinomas originating from the uterine cervix. HPV E6 and E7 oncogenes have been shown to cooperate with ras oncogenes to fully transform human epithelial cells. We investigated the effect of the Ha-ras oncogene on the transcriptional activity of HPV-18 and found that it induced the transcriptional activity of the viral promoter, whereas the normal gene had only a minimal effect. However, transfection of the normal Ha-ras gene and simultaneous inhibition of protein phosphatase sensitive to okadaic acid (OA) resulted in a cooperative transactivation of the viral promoter. When cloned upstream of a minimal promoter, the AP-1 binding sites present in the viral promoter conferred transcriptional responsiveness to Ha-ras and OA. Furthermore, HeLa cell clones permanently expressing the Ha-ras oncogene or high levels of the normal gene exhibited a twofold to threefold increase in E6*E7/E1 and E6*E7 transcripts. We propose that both Ha-ras and a protein phosphatase sensitive to OA regulate HPV oncogene expression through modulation of AP-1 activity and suggest that increased levels of E6 and E7, resulting from activated viral transcription in the presence of ras oncogenes, may in part explain the observed cooperation between these viral and cellular oncogenes in the transformation of human cells.

Testosterone concentration in blood serum of buffalo bulls during 24 hours in winter and summer seasons

Concentraçöes de testosterona foram determinadas por radioimunoensaio em 30 amostras de soro sanguíneo obtidas cinco vezes durante 24 horas, de 6 búfalos adultos Jaffarabadi x Mediterrâneo. As amostras foram obtidas durante um dia do inverno e um dia do veräo de 1991. As concentraçöes de testosterona variaram de 0,10 a 1,36 ng/ml no inverno e de 0,10 a 2,454 ng/ml no veräo. Valores máximos foram obtidos às 6,00 horas (0,52 ng/ml) no veräo e 0,82 ng/ml no inverno, ocorrendo entäo duas quedas abruptas, a primeira às 12 horas (0,37 ng/ml) no veräo e 0,21 ng/ml no inverno e a segunda 24 horas (0,17 ng/ml) no veräo e 0,49 ng/ml no inverno. No veräo, níveis mais altos de testosterona sérica foram observados durante o dia

Early promoters of genital and cutaneous human papillomaviruses are differentially regulated by the bovine papillomavirus type 1 E2 gene product.

The physical state of the human papillomavirus (HPV) genome is usually different in malignant lesions of the skin, in which it is generally found in episomal form, and genital mucosa, in which it is frequently integrated with disruption of the E2 gene. Using chimeric or natural HPV promoters in the presence of the bovine papillomavirus type 1 E2 gene product, we observed transcription activation or repression, depending on the distance of E2-binding motifs from the start site. We found a clear difference in the positions of E2-binding motifs in cutaneous and genital HPVs that may partly explain the selective pressure for genome integration of genital HPV types in malignant lesions.