Expression of the simian virus 40 large tumor antigen (Tag) and formation of Tag-p53 and Tag-pRb complexes in human brain tumors

BACKGROUND. The presence of simian virus 40 (SV40) in human brain tumors re mains a controversial issue. Even if SV40 does exist in brain tumors, the q uestions of whether it is associated with brain tumorigenesis and by what m echanisms are unknown. METHODS. SV40 large tumor antigen (Tag) was investigated by immunoprecipita tion, silver staining, and Western blot analysis in 65 brain tumor cases an d 8 cases of normal brain tissue. Tag-p53 and Tag-pRb complexes were screen ed by immunoprecipitation and Western blot analysis in 18 and 15 Tag positi ve tumor tissues, respectively. RESULTS. Tag was found in all 8 cases of ependymoma and 2 cases of choroid plexus papilloma, 90% of pituitary adenoma cases (9 of 10), 73% of astrocyt oma cases (11 of 15), 70% of meningioma cases (7 of 10), 50% of glioblastom a multiforme cases (4 of 8),and 33% of medulloblastoma cases (2 of 6). Five oligodendroglioma cases, 1 pineocytoma case. and 8 cases of normal brain t issue were negative for Tag. The Tag-p53 complex was detected in all 18 Tag positive tumors tested and the Tag-pRb complex was detected in all 15 Tag positive tumors tested. CONCLUSIONS. SV40 Tag not only is expressed in brain tumors; it also can fo rm specific complexes with tumor suppressors p53 and pRb. SV40 is correlate d with brain tumorigenesis. The inactivation of p53 and pRb due to the form ation of Tag-p53 and Tag-pRb complexes possibly is a significant mechanism in the etiopathogenesis of brain tumors. Cancer 1999;86:2124-32. (C) 1999 A merican Cancer Society.