Malignant Transformation of Fanconi Anemia Complementation Group D2-deficient (Fancd2−/−) Hematopoietic Progenitor Cells by a Single HPV16 Oncogene

Aim: To demonstrate that Fanconi anemia complementation group D2-deficient (Fancd2−/−) hematopoietic progenitor cell lines can be transformed by transfection with a plasmid containing either the E6 or E7 oncogene of human papillomavirus (HPV) to generate malignant plasmacytoma-inducing cell lines. Materials and Methods: In order to determine whether a single HPV type 16 (HPV16) oncogene induced malignant transformation, Fancd2−/− and Fancd2+/+ interleukin 3 (IL3)-dependent hematopoietic progenitor cell lines were transfected with plasmids containing E6 or E7 oncogene, or control empty plasmid. Results: Fancd2−/− but not Fancd2+/+ cells were transformed into malignant IL3-independent cells by both E6, and E7 oncogenes, but not by empty plasmid. Hematopoietic cell lines and tumors induced by Fancd2−/− E6 and Fancd2−/− E7 cell lines were positive for each respective HPV RNA and protein. Conclusion: A single HPV16 oncogene is adequate to produce malignant transformation of Fancd2−/− hematopoietic cells.

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