We investigated the transforming activity of human papiflomavirus type 8 (HPV8) by expressing all early open reading frames from a heterologous promoter in different rodent fibroblast lines. Morphological transformation was observed only in G418-selected mouse C127 and Rat 1 cells containing an intact E6-coding region. E6 of HPV8 did not transform NIH 3T3 cells as did E6 of bovine papillomavirus type 1. C127 cells transformed by E6 were anchorage independent and had a reduced serum requirement but did not form tumors in nude mice. E7 of HPV8 showed no transforming potential, in contrast to E7 of HPV18 and HPV16. It was, however, able to complement an E7 mutant of bovine papillomavirus type 1 with a defect in high-copy-number DNA maintenance. The data indicate that the expression of the HPV8 E6 open reading frame is sufficient to induce morphological transformation in rodent fibroblasts, whereas E7 is involved in the replication of the viral DNA.
The correlation between tumor volume of untreated tumor-bearing nude mice and serum concentration of prostatic acid phosphatase (PAP/RIA) was studied in the hormone-dependent serially transplantable human prostatic tumor models PC-82 and PC-EW. The normal serum level of PAP in control male nude mice without tumor was found to be 0.9 +/- 0.3 ng/ml. Elevated PAP serum concentrations were never found in animals without tumor (a highly specific diagnostic technique). A close correlation was observed between the concentration of PAP in the serum (range 0.3 to 154 ng/ml) and the tumor volume (range 10.0 to 6,530 mm3) of 104 untreated mice bearing a PC-82 or PC-EW human prostatic tumor. This correlation was comparable in both tumor lines (p less than 0.001). The positive effect of endocrine manipulation which resulted in tumor diameter decrease or growth arrest with regressive histological patterns, showed the normal PAP serum level, too. After successful treatment PAP was found to be normal, independent from the residual tumor mass. By contrast, in the event of only retarded tumor growth, the PAP level still correlated with the tumor burden.
The biotin-avidin immunoperoxidase assay was used to evaluate the expression of several prostate carcinoma-associated markers in formalin-fixed paraffin-embedded tissue sections of three human prostate nude mouse heterotransplant lines PC-82, PC-EW, and PC-EG. In addition to monoclonal antibodies to PSA and PAP, monoclonal antibodies to five other potentially useful markers for prostate carcinomas (TURP-27, Leu-7, 7E11-C5, PSP-19, and PD41) were tested. Tissues from two or more transplant passages were evaluated. The human prostate target antigens were found to be expressed by one or more of the three heterotransplant lines. The PC-82 and PC-EW lines were the most efficient in terms of expression of multiple prostate carcinoma-associated markers and percentage of tumor cells positive for a given prostate antigen. The staining pattern of each marker, in terms of staining intensity, number of tumor cells stained, and staining location, i.e., membrane, cytoplasmic, or ductal secretions, was similar to what has been observed in tissue sections from human prostate carcinomas. The lack of an appropriate model for evaluating the preclinical potential of these Mabs (especially TURP-27, PSP-19, and PD41) makes the findings of this study of considerable importance, and suggests that these human prostate xenografts may be useful models for exploring the diagnostic and therapeutic potential of these anti-prostate carcinoma monoclonal antibodies.
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