Differential suppression of the tumorigenicity of HeLa and SiHa cells by adeno-associated virus

Adeno-associated virus (AAV) is well known for suppression of oncogenesis in rodents, but its inhibitory effects on human carcinoma are less well understood. We report the differential ability of AAV to inhibit the tumorigenicity of two human cervical carcinoma cell lines. The wild-type AAV-2 DNA carried by a pSV2Neo vector was transfected into HeLa cells, which contain 50 copies of human papillomavirus type 18 (HPV-18), and SiHa cells, which contain 1-2 copies of HPV-16. About 1-3 copies of AAV genome were introduced per cell. AAV transfection moderately reduced the growth rate and anchorage-independent activity of the cells. In nude mice, the size of tumours arising from SiHa cells was reduced by 87%, in contrast to no reduction in tumour size arising from HeLa cells. This suggests that the differential suppression exerted by AAV may be due to differences in HPV copy number. To define the region that is responsible for the oncosuppression, mutation analyses were conducted. The results of nude mice assays showed that both the replication gene and inverted terminal repeats of AAV were important for the inhibition. This study may provide a model system for further studies on the underlying mechanism of AAV oncosuppressive activity.