Cotransfection of HPV-18 and v-fos DNA induces tumorigenicity of primary human keratinocytes.
Human keratinocytes were cotransfected with the FBJ/R v-fos oncogene and the HPV-18 genome and selected on the basis of their resistance to inducers of terminal differentiation. Unlike keratinocytes immortalized by HPV-18 DNA alone, the HPV-18/v-fos transformants exhibited prominent intracellular vacuolization and formed progressively growing, squamous cell tumors when injected subcutaneously into nude mice. Cytogenetic analysis of two clonally selected transformed cell lines (18/fos clone 1 and 18/fos clone 2) revealed minimal alterations in karyotype, although a consistent rearrangement of chromosome 10, iso(10q), was observed. Further analysis of 18/fos clone 1 confirmed the expression of the fos gene as well as the HPV-18 E7 protein. Alterations in fos gene expression, which appear to be an important facet of epidermal differentiation in vivo, could potentially contribute to the malignant progression of HPV immortalized cells.
Department of Pathology, Georgetown University Medical School, Washington, DC.
X F
XF
Pei
J M
JM
Meck
D
D
Greenhalgh
R
R
Schlegel
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003582:Cytogenetics; D004268:DNA-Binding Proteins; D016762:Genes, fos / Q000235:genetics*; D016679:Genome, Viral; D006801:Humans; D015603:Keratinocytes / Q000648:ultrastructure; D051379:Mice; D008819:Mice, Nude; D016761:Oncogene Proteins v-fos / Q000096:biosynthesis; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis; D027383:Papillomaviridae / Q000235:genetics*; D012878:Skin Neoplasms / Q000648:ultrastructure; D014162:Transfection
D004268:DNA-Binding Proteins; C052633:E7 protein, Human papillomavirus type 18; D016761:Oncogene Proteins v-fos; D009856:Oncogene Proteins, Viral