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

Abstract

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.

Keywords: E6 and E7 oncogene; Fanconi anemia; Human Papillomavirus.