title: Nfe2l3 (Nrf3) deficiency predisposes mice to T-cell lymphoblastic lymphoma.
abstract: We have previously generated mice deficient for Nfe213 (NF-E2 p45 related factor 3 or Nrf3), a member of the cap 'n' collar family of basic-leucine zipper transcription factors. To examine whether Nrf3 is involved in chemical-induced carcinogenesis, we exposed the mice to benzo[a]pyrene (B[a]P), a carcinogen found in cigarette smoke. Contrary to wild-type mice, Nrf3-null animals are highly susceptible to B[a]P, exhibiting significantly increased mortality. Pathology analysis of affected tissue sections revealed a high incidence of T-cell lymphoblastic lymphoma in B[a]P-treated Nrf3(-/-) mice. Lymphoblastic lymphoma occasionally metastasized into the lung as demonstrated by perivascular malignant lymphocytic infiltration. Together, our studies show that the absence of Nrf3 predisposes mice to lymphoma development, suggesting a protective role of this transcription factor in hematopoietic malignancies. Our data demonstrate the first in vivo function of Nrf3 and its link to tumor development. Nrf3-deficient mice may serve as a preclinical mouse model to study carcinogen-induced lymphomagenesis.
authors.affiliation: Lady Davis Institute for Medical Research and Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Grégory
authors.initials: G
authors.lastname: Chevillard
authors.forename: Marilene
authors.initials: M
authors.lastname: Paquet
authors.forename: Volker
authors.initials: V
authors.lastname: Blank
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency* / Q000235:genetics; D001564:Benzo(a)pyrene / Q000633:toxicity; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C117963:NFE2L3 protein, human; C485120:Nrf3 protein, mouse; D001564:Benzo(a)pyrene