Comparison of the in vitro transforming activities of human papillomavirus types.

Abstract

The association of certain human papillomavirus (HPV) types with the majority of human cervical carcinomas suggests a role for the virus in the development of this type of cancer. In this paper, we have examined the transforming properties of several HPV types where the early region genes of the virus are under the control of a strong heterologous promoter and show that major differences exist between the HPV types in their ability to transform primary rat kidney epithelial cells in conjunction with an activated ras oncogene. Those HPV types most commonly found in carcinomas–types 16, 18, 31 and 33–are capable of co‐operating with ras to transform primary cells, but those types most commonly found in benign lesions–types 6 and 11–are not. We further demonstrate that the E7 gene of HPV16 by itself is sufficient to co‐operate with activated ras to produce transformed cells which are tumorigenic in immunocompetent animals.

Epidemiologic Classification of Human Papillomavirus Types Associated with Cervical Cancer

“…Types 16 and 18, as well as types 31 and 33, but not types 6 and 11, can induce immortalization of primary human keratinocytes and rat kidney cells. [28][29][30] The prevalence of multiple HPV infections varies in relation to the method used to detect HPV DNA. 10 In our study, the use of the PCR assay with the GP5+/6+ primer system may have led to an underestimation of the prevalence of multiple infections.…”

Inhibition of E6 induced degradation of p53 is not sufficient for stabilization of p53 protein in cervical tumour derived cell lines

“…Establishment of HPV-16 immortalized cell lines W12, V1/G and AC89/E2 has been described previously (Stanley et al, 1989;Bouvard et al, 1996;Storey et al, 1992). Keratinocyte cell lines were grown in a 3 : 1 mixture of DMEM and Ham F12 medium, supplemented with 10% foetal calf serum, 10 ng/mL epidermal growth factor, 10 710 M cholera toxin and 0.4 mg/ mL hydrocortisone at 378C and 10% CO 2 .…”

The human papillomavirus (HPV)-6 and HPV-16 E5 proteins co-operate with HPV-16 E7 in the transformation of primary rodent cells

“…HPV-6 DNA is found in genital warts and low grade cervical lesions whereas HPV-16 DNA is frequently found in high grade lesions and in carcinomas (Diirst et al, 1983;Gissmann et al, 1983). The HPV-16 E6 and E7 genes are retained and expressed in cervical tumours (Schwarz et al, 1985;Smotkin & Wettstein, 1987;Androphy et al, 1987;Banks et al, 1987) and represent the major transforming genes of the virus (Matlashewski et al, 1987;Phelps et al, 1988;Storey et al, 1988;Storey & Banks, 1993). In contrast, the HPV-16 E5 gene is often lost as a result of viral integration into the host genome (Schwarz et al, 1985;Yee et al, 1985).…”

“…The HPV-16 E7 gene can co-operate withfos or ras to transform primary baby mouse kidney (BMK) cells (Crook et al, 1988) and with ras to transform BRK cells (Storey et al, 1988). Recently, we have shown that cooperation between the HPV-16 E7 and E5 genes can result in an increased proliferative capacity in primary BRK cells which is enhanced in the presence of E G F (Bouvard et al, 1994).…”