title: Evolution of malignant plasmacytoma cell lines from K14E7 Fancd2-/- mouse long-term bone marrow cultures.
abstract: We tested the effect of expression of the Human Papilloma Virus (HPV E7) oncogene on hematopoiesis in long-term bone marrow cultures (LTBMCs) derived from K14E7 (FVB) Fancd2-/- (129/Sv), K14E7 Fancd2+/+, Fancd2-/-, and control (FVB X 129/Sv) Fl mice. K14E7 Fancd2-/- and Fancd2-/- LTBMCs showed decreased duration of production of total nonadherent hematopoietic cells and progenitors forming day 7 and day 14 multilineage CFU-GEMM colonies in secondary cultures (7 wks and 8 wks respectively) compared to cultures from K14E7 Fancd2+/+ (17 wks) or control mice (18 wks) p < 0.0001. Marrow stromal cell lines derived from both K14E7 Fancd2-/- and Fancd2-/- cultures were radiosensitive, as were IL-3 dependent hematopoietic progenitor cell lines derived from K14E7 Fancd2-/- cultures. In contrast, Fancd2-/- mouse hematopoietic progenitor cell lines and fresh marrow were radioresistant. K14E7 Fancd2-/- mouse freshly explanted bone marrow expressed no detectable K14 or E7; however, LTBMCs produced K14 positive factor-independent (FI) clonal malignant plasmacytoma forming cell lines in which E7 was detected in the nucleus with p53 and Rb. Transfection of an E6/E7 plasmid into Fancd2-/-, but not control Fancd2+/+ IL-3 dependent hematopoietic progenitor cell lines, increased cloning efficiency, cell growth, and induced malignant cell lines. Therefore, the altered radiobiology of hematopoietic progenitor cells and malignant transformation in vitro by K14E7 expression in cells of the Fancd2-/- genotype suggests a potential role of HPV in hematopoietic malignancies in FA patients.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, 15232 PA, USA.
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, 15232 PA, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Hou
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, 15232 PA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.affiliation: Division of Laboratory Animal Resources, University of Pittsburgh, Pittsburgh, 15260 PA, USA.
authors.forename: Lora
authors.initials: L
authors.lastname: Rigatti
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, 15232 PA, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, 15232 PA, USA.
authors.forename: Darcy
authors.initials: D
authors.lastname: Franicola
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, 15232 PA, USA.
authors.forename: Aranee
authors.initials: A
authors.lastname: Sivanathan
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, 15232 PA, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000172:deficiency / Q000235:genetics*; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D010954:Plasmacytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors
chemical_list: D052236:Fanconi Anemia Complementation Group D2 Protein; D053547:Keratin-14; D050725:Papillomavirus E7 Proteins
keywords: E7; Fancd2−/− mice; HPV oncogene; human papillomavirus; Fanconi anemia