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.
Pei
X F
XF
Department of Pathology, Georgetown University Medical School, Washington, DC.
Meck
J M
JM
Greenhalgh
D
D
Schlegel
R
R
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