Expression of the Fanconi anemia group C gene in hematopoietic cells is not influenced by oxidative stress, cross-linking agents, radiation, heat, or mitotic inhibitory factors

P. A. Tower, T. A. Christianson, S. T. Peters, M. L. Ostroski, Maureen Hoatlin, A. J. Zigler, Michael Heinrich, R. K. Rathbun, W. Keeble, G. R. Faulkner, Jr Bagby G.C.

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The Fanconi anemia group C gene (FAC) encodes a 63-kDa protein that plays a role in the growth and differentiation of hematopoietic progenitor cells and in cellular resistance to bifunctional cross-linking agents. The function of the gene product is unknown, as are the factors that govern expression of the gene itself. Seeking to associate a function of this protein with a general metabolic pathway, we attempted to identify factors that induce or repress expression of the gene encoding it. Using two plasmids from which mutant FAC mRNA molecules were transcribed in vitro to serve as competitor mRNAs in quantitative-competitive reverse transcriptase-polymerase chain reaction analysis and novel rabbit antisera raised to recombinant FAC proteins, we quantified gene expression in human hematopoietic cells. We determined that FAC is expressed constitutively in unstimulated normal peripheral blood mononuclear leukocytes, in Epstein-Barr virus (EBV)- transformed B lymphocytes, and in the factor-dependent human myeloid leukemic cell line MO7e at levels of approximately 2000, 200, and 200 FAC mRNA molecules/cell, respectively, and in CD34+ cells from normal human bone marrow at approximately 2000 FAC mRNA molecules/cell. Neither mRNA nor protein increased in any of the cells studied after exposure to mitomycin C, diepoxybutane, hydrogen peroxide, gamma radiation, heat, transforming growth factor-β, or interferon-γ. Using these sensitive methods, we confirmed that the FAC gene is constitutively expressed, even in the face of extracellular factors for which the gene product is a known effector of resistance. We conclude that the protective functions of the FAC gene product do not depend upon stressor-induced FAC gene expression.

Original languageEnglish (US)
Pages (from-to)19-26
Number of pages8
JournalExperimental Hematology
Volume26
Issue number1
StatePublished - 1998

Fingerprint

Fanconi Anemia
Oxidative Stress
Hot Temperature
Radiation
Messenger RNA
Gene Expression
Genes
Mononuclear Leukocytes
Proteins
Gamma Rays
Transforming Growth Factors
Mitomycin
Myeloid Cells
Hematopoietic Stem Cells
Metabolic Networks and Pathways
Reverse Transcriptase Polymerase Chain Reaction
Human Herpesvirus 4
Recombinant Proteins
Interferons
Hydrogen Peroxide

Keywords

  • Fanconi anemia
  • Gene expression
  • Hematopoiesis
  • Polymerase chain reaction
  • Reverse transcription

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Expression of the Fanconi anemia group C gene in hematopoietic cells is not influenced by oxidative stress, cross-linking agents, radiation, heat, or mitotic inhibitory factors. / Tower, P. A.; Christianson, T. A.; Peters, S. T.; Ostroski, M. L.; Hoatlin, Maureen; Zigler, A. J.; Heinrich, Michael; Rathbun, R. K.; Keeble, W.; Faulkner, G. R.; Bagby G.C., Jr.

In: Experimental Hematology, Vol. 26, No. 1, 1998, p. 19-26.

Research output: Contribution to journalArticle

Tower, P. A. ; Christianson, T. A. ; Peters, S. T. ; Ostroski, M. L. ; Hoatlin, Maureen ; Zigler, A. J. ; Heinrich, Michael ; Rathbun, R. K. ; Keeble, W. ; Faulkner, G. R. ; Bagby G.C., Jr. / Expression of the Fanconi anemia group C gene in hematopoietic cells is not influenced by oxidative stress, cross-linking agents, radiation, heat, or mitotic inhibitory factors. In: Experimental Hematology. 1998 ; Vol. 26, No. 1. pp. 19-26.
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AU - Zigler, A. J.

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